Proteomic Analysis on Myocardial Injury Induced by Hyperuricemia Rats

Proteomic Analysis on Myocardial Injury Induced by Hyperuricemia Rats | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Proteomic Analysis on Myocardial Injury Induced by Hyperuricemia Rats Zubiya Yusufu, Shenshen Wang, Dilinuer Maimaitiyiming, Xiang Ma, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8268831/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Hyperuricemia (HUA) has been confirmed to be closely associated with the occurrence and progression of cardiovascular diseases; however, the specific molecular mechanisms through which it induces myocardial injury remain to be fully elucidated. This study aimed to investigate the cardiotoxic effects of HUA and explore associated proteomic alterations by establishing a HUA rat model. Myocardial injury was assessed by measuring serum levels of uric acid (UA), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), and cardiac troponin T (cTnT). Differential protein expression profiles were analyzed using proteomic techniques. The results showed significantly elevated levels of UA, CK, CK-MB, and cTnT in the model group. A total of 40 differentially expressed proteins were identified, including 11 up-regulated and 30 down-regulated proteins, such as CCDC88C, LPIN1, and SDHD, which are associated with inflammatory response, oxidative stress, and mitochondrial dysfunction. GO functional analysis indicated that these proteins are involved in biological processes including myocardial hypertrophy, contraction, and fibrosis. This study reveals potential mechanisms by which HUA may contribute to myocardial injury at the protein level, providing a theoretical basis for further research. Hyperuricemia Protein Myocardial injury Proteomic Troponin Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 1. Introduction In recent years, studies showed that Genetic and environmental factors combined contributed to the development of hyperuricemia and gout [ 1 ]. Hyperuricemia has been associated with many diseases such as cardiovascular diseases, stroke, chronic kidney disease, and hypertension [ 2 – 6 ]. Is there any definite gene correlated between hyperuricemia and cardiovascular disease still be not clear. In this study, we aimed to determine whether any gene protein in high uric cid related to myocardial injury and to identify the molecular pathways implicated in this process. For this, we used yeast extract powder (YEP) and oxonic acid potassium salt (OA) establish a hyperuricemia rat model. Monitering uric acid (UA) and Troponin (TNT), observing myocardial cells pathological changes compared and using TMT-based quantitative proteomics to identificated differential proteins of cardiomyocyte in hyperuricemia rats, analyzed GO functional and KEEG functional to determined these proteins irrelated pathway. 2. Materials and Methods 2.1. Animals Twenty-four male Sprague-Dawley (SD) rats, weighing 203.8 ± 32.15 g, were provided by the Animal Experiment Center (SPF-grade) of Xinjiang Medical University. All animals were acclimatized for one week before the experiment, with body weight measured twice weekly for drug dosage adjustment. The animals were bred and maintained in the institutional animal center under standard conditions (12 h light/dark cycle, 22 ± 2 °C, 50–60% humidity), with ad libitum access to food and water. The animals used in this study were uniformly bred and supplied by the institutional animal center, and did not in-volve privately owned or farm-sourced animals; therefore, obtaining owner consent was not applicable. 2.2. Drug intervention A total of 24 male SD rats were randomly divided into 2 groups (12 rats/group). To establish hyperuricemia models, rats were intragastrically administered YEP (production batch no. 20090705; Beijing Aoboxing Biological Technology Co, Ltd, Beijing, China,mixed with standard feed at a proportion of 1:4), and intraperitoneally injected with 200 mg/kg/day OA (production batch no. 20120312; Sigma‐Aldrich Co, Munich, Germany). 2.3. Specimen collection Blood samples (2 ml) were collected in the morning at 0, 2, and 4 weeks. Prior to blood collection via orbital sinus/plexus puncture (a common method often referred to as “retro-orbital bleeding”), rats were briefly anesthetized by inhalation of isoflurane to ensure humane handling and eliminate procedural pain. A standard induction chamber was used with 4–5% isoflurane in oxygen (flow rate: 1–2 L/min) for rapid induction (within 2–3 minutes). Once the righting reflex was lost, the rat was quickly transferred, and anesthesia was maintained at a surgical plane using a nose cone delivering 2–3% isoflurane. The entire blood collection procedure was completed within 1–2 minutes per animal to minimize anesthesia duration and physiological stress. This inhalation anesthesia protocol is widely adopted in rodent studies for brief invasive procedures and aligns with established guidelines for laboratory animal welfare. Following collection, blood samples were allowed to clot naturally and then centrifuged at 1509.3 × g for 15 min (Allegra 64R, Beckmann Coulter, Miami, FL, USA). The separated plasma was aliquoted and stored at −80°C until analysis for UA and TnT levels. 2.4. HE staining After successful fixation of myocardial tissue, 25px needs to be trimmed ✖️ 25px ✖️ 5px, put it into the embedding box, rinse with running water (remove the fixative in the tissue) for 30 minutes. As for the dehydration of alcohol with different concentrations, the alcohol with low concentration to high concentration is generally used as the dehydrating agent to gradually remove the water in the tissue block. Then put the tissue block in the transparent agent xylene which is soluble in both alcohol and paraffin for transparency, and replace the medium alcohol of the tissue block with xylene, then the tissue block can be immersed in wax for embedding. Put the transparent tissue block in the melted paraffin and put it into the wax dissolving box for heat preservation. After the paraffin is completely immersed in the tissue block, it is embedded, cooled and solidified into blocks. Only when the embedded tissue blocks become hard can they be cut into very thin sections on the microtome. Fix the embedded wax block on the slicer and cut it into thin slices, generally 5-8 microns thick. The cut slices are often wrinkled. They should be put into heated water for ironing, and then pasted onto the glass slides. They should be dried in a 45 ℃ constant temperature oven, dewaxed, watered, and dyed. 2.5. Ultrastructure of myocardial celles After the pancreatic tissue added with electron microscope fixative was fixed for 2-4 hours, it was rinsed 3 times with 0.1M phosphate buffer PB (PH7.4) for 15 minutes each time. After that, 1% osmic acid was used to fix it at room temperature of 20 ℃ for 2 hours, and 0.1M phosphate buffer PB (PH7.4) was used to rinse it for 3 times, each time for 15 minutes. After that, the pancreatic tissue was dehydrated with 50% - 70% - 80% 90% - 95% alcohol for 15 minutes each time. Penetrate with acetone 812 embedding agent=1:1 for 2-4 hours, acetone: 812 embedding agent=2:1 overnight, pour the pure 812 embedding agent into the embedding plate 5-8 hours later, insert the sample into the embedding plate, then put it in the 37 ℃ oven overnight, and then polymerize it in the 60 ℃ oven for 48 hours. Pancreatic tissue block or tissue slice shall be cut thin enough (no more than 80 nm). After sectioning, use uranium lead double staining (2% uranium acetate saturated alcohol solution, lead citrate, each staining for 15 minutes) to dry the section interpretation overnight. Finally, observe under fluoroscopy electron microscope and collect images for analysis. 2.6. Protein extraction The Myocardial tissue sample was added with liquid nitrogen for grinding, and the frozen powder was transferred to the EP tube.Add 1.0mL lysate into the sample powder, and lyse it with ultrasonic for 10min on ice. Ultrasonic condition: pulse on 5s; pulse off 15s; power 180W ；Preparation of cracking solution buffer: 7M urea, 4% SDS, 30mM HEPES, 1mM PMSF, 2mM EDTA, 10mM DTT, 1X protease inhibitor.After ultrasound, centrifugate 10000g at 4 ℃ for 30 minutes, and take the supernatant and protein was quantified by using BCA method.100μg protein solution of each sample is transferred to a new EP tube, and 100mM triethylammonium bicarbonate (TEAB) is added to it up to 100 μl. Add DTT to the final concentration to10mM. 55 ℃ water bath for 1h. After removal, add IAA rapidly to the final concentration to 35mM, and left the dark room for 1h. Add more than 4 times volume of sample solution with precooled acetone, and precipitate at - 20 ℃ for more than 3h. Centrifuge in 4 ℃, 20000g, 30min, and take the sediment.Add 1ml of 50% acetone and 50% of ethanol solution to suspend and precipitate, and precipitate at - 20 ℃ for more than 3h. Centrifuge, 4 degrees, 20000g, 30min, and take the sediment. and this step was repeated twice. Then Add 100 µ L 100mM TEAB solution for mixing. 2.7. Proteolysis Protein precipitation adding 100 μ L 100mM TEAB, 1 µ g/µ l of Trypsin, and to per 100ug of protein substrate add 1.0 µg of enzyme, soaked in 37℃water at 37 for 4h, and then add 1.0 µ g of Trypsin，soaked in 37℃water at 37 for.Centrifuge 5000g solution to the bottom of EP tube.Peptide solution was dried into powder by freeze dryer，then take 1 µ g enzymolysis sample from each sample to 1h LC-MS analysis. 2.8. Peptide labeling After the peptide solution iwas freeze-dried, add 100 μ L 50mM TEAB solution to dissolution.TMT10 labeling reagent was balanced to room temperature.Add 41 µ L acetonitrile into each tube of labeling reagent, vortex it for 1 min, and centrifuge it to the bottom of the tube.The labeling reagents are added to the corresponding peptide solution according to the labeling information table, and different samples are labeled with isotopes of different sizes.After the peptide segment was mixed with the labeling reagent, it is thrown to the bottom of the tube and left at room temperature for 2h.1 ug of each sample was mixed for labeling efficiency test.Mix the marked samples into one sample and transfer it to a new EP tube.Freeze and dried the labeled sample. 2.9. Desalination of TMT labeled peptide Use 400 µ L 0.1% TFA, 0.5% acetonitrile solution to dissolve the dried mixed labeled peptide.Use 200 µ L 0.1% TFA and 60% acetonitrile to activate the desalting column.Use 400-600 µ L 0.1% TFA, 1% acetonitrile solution to balance the desalination columnAdd the redissolved sample into the desalting column, the labeled peptide was captured by the desalting column, and other non hydrophobic small molecules such as salt flow out and discard.Add 200 µ L 0.1% TFA and 0.5% acetonitrile solution to clean the desalting column and remove residual salts. Add 300 µ L 0.1% TFA, 60% acetonitrile solution, make the liquid flow slowly through the desalting column, elute the peptide segment, and use a new EP tube to collect the elution solution.Freeze end dried the eluting solution to remove acetonitrile. 2.10. Separation of TMT labeled Peptides by High pH Reversed Phase Liquid Chromatography High pH mobile phase A was 10mM ammonium formate, pH=10.0 (adjusted by chromatographic pure ammonia); High pH mobile phase B was 10mM ammonium formate[7], 90% acetonitrile, pH=10.0 (adjusted by chromatographic pure ammonia).The TMT labeled peptide powder was desalted with 52 µ L A-phase solvent. Ultra high performance chromatographic column (BEH C18 1.7 µ m, 2.1 × 150mm). The flow rate is 250 µ L/min, and the ultraviolet detection is at 215 nm.From 2 minutes, collect 1 tube every 1.0 minutes. According to the chromatographic peak type, the fractions are combined into 12 fractions. 2.11. Mass Spectrum detection The spray voltage of the ion source was 2.3kv, the heating capillary of Orbitrap fusion mass spectrometer was set at 320 ℃, and the data dependent mode was adopted to automatically switch between MS and MS / MS for acquisition. The full scan MS uses Orbitrap to perform the first scanning. The scanning range is m/z 400-1600, and the resolution was set to 120000 (m/z 200 places). The maximum ion introduction time is 50ms, the Automatic gain control (AGC) is set to 1x106, and then in 3 seconds, the parent ions that meet the cascade (MS/MS) fragmentation conditions were broken by using High energy C-trap dissociation (HCD) and scanned with orbitrap, with the scanning resolution set to 15000. The scanning range is automatically controlled according to the mass charge ratio of the parent ion. The minimum scanning range is fixed at m/z=110, and the maximum scanning range was 2000. The minimum ion strength value for MS/MS is set to 50000, and the scanning resolution is 30000. In MS/MS, the maximum ion introduction time was 80ms, the AGC control was set to 1.0x105, and the parent ion selection window was set to 1.6 Dalton. MS/MS collection was carried out for ions with 2, 3 and 4 charges. The dynamic exclusion iwas set to conduct MS/MS once in 10 seconds for each parent ion, and then exclude 35% of the collision energy in 30 seconds.After inputting the mass spectrum data into Proteome Discoverer software (PD) (version 2.4.0.305, thermo Fisher Scientific), the software first screens the mass spectrum.Qualitative and quantitative database searchThe spectrogram extracted by Proteome Discoverer is searched by the Sequest HT search engine. After the search, PD software conducts quantitative analysis according to the search results and the spectrogram screened in the first step. UniprotKB database (species Rattus norvegicus (Rat), 2021-07-25, Total entries 36153; reviewed entries 8106; unreviewed entries 28047。Database link: https://www.uniprot.org/taxonomy/10116 False positive rate of peptide and protein in search results FDR<1%.Differential protein was screened by the ratio and P value. Screening criteria: if fold change ≥ 1.2 and P ≤ 0.05, then the protein was over-represented; if P ≤ 0.05, then the protein and fold change ≤ 0.833 was under-represented [8]. After pretreatment, 4744 detection proteins were retained. 2.12. Statistical analysis All experimental data are expressed the mean ± standard deviation (SD), The student‘s t- test was used to compare categorical variables between the two groups. statistical analysis was performed with the SPSS software version 26.0. P<0.05 was considered to indicat a statistically significant difference. 2.13. Anesthesia and Euthanasia Protocol All rats were euthanized upon completion of the 4-week hyperuricemia modeling experiment to collect myocardial tissue for subsequent proteomic analysis. Prior to euthanasia, the animals were deeply anesthetized via intraperitoneal injection of pentobarbital sodium (60 mg/kg). The depth of anesthesia was confirmed by the loss of corneal and pedal withdrawal reflexes. After the animals had fully lost consciousness (approximately 5–10 minutes post-injection), euthanasia was performed by cervical dislocation. 3. Results 3.1. The changes of serumUA,CK,CK-MB and TnT indexes in two groups of animal After 4 weeks of pharmacological .intervention, serum UA levels in the model group were significantly elevated compared to the control group, with a statistically significant difference (P < 0.05). Concurrently, serum levels of CK, CK-MB, and TnT in the model group were also markedly increased, demonstrating statistically significant differences compared to the control group (Table 1). Table1 The changes of serum UA,CK,CK-MB and TnT indexes in two groups of animal （x±s） Groups 0week 4week t value P value control （ n =12） model（ n =12） t value P value control （ n =12） model （ n =12） Uric acid（UA,µmol/L） 41.63± 4.93 42.47± 4.35 0.312 0.761 42.28± 6.46 469.28± 62.09 16.756 ＜0.001 aa Creatine Kinase（CK,U/L） 87.53± 45.78 104.66± 53.67 0.595 0.565 116.05± 47.58 900.83± 423.13 4.515 0.001 Creatine Kinase Isoforms(CK-MB, U/L） 18.47± 4.03 13.03± 4.80 2.128 0.059 15.82± 7.50 365.83± 74.78 11.407 ＜0.001 aa TroponinT(TnT,ug/L) 0.009± 0.001 0.009± 0.001 0.269 0.794 0.008± 0.003 1.316± 0.370 8.669 ＜0.001 aa Model group vs control group a P ＜0.05； aa P ＜0.01 3.2 Proteomics Analysis The reliability of identified proteins was mainly derived from mass spectrometry (MS) analysis. The 4744 proteins were found in both the control and the treated group. Of the 4744 proteins, 4704 proteins were detected in both groups. Compared to control group，in model group the proteomic landscape reveals 11 upregulated proteins and 30 downregulated proteins (Fig. 1,2;Table 3). upregulated proteins including inflammation related protein, myocardial injury related protein and gout related protein. Table 3 Differential Protein Information Protein name Protein discription FC Log2FC P value state CCDC88C Coiled-coil domain-containing 88C 1.5736 0.6540 0.0085 up Lpin1 Lipin 1 1.3566 0.4399 0.0201 up Spg11 SPG11 vesicle-trafficking-associated 1.3347 0.4165 0.0449 up SDHD Succinate dehydrogenase 1.3005 0.3791 0.0015 up Rap2a RAS related protein 2a 1.2942 0.3721 0.0249 up Tacc1 Transforming, acidic coiled-coil-containing protein 1 1.2503 0.3228 0.0013 up Cox7b Cytochrome c oxidase subunit 7B 1.3005 0.3211 0.0153 up MRPS7 28S ribosomal protein S7 1.2444 0.3154 0.0039 up Erlec1 Endoplasmic reticulum lectin 1 1.2406 0.3108 0.0207 up NRBP1 Nuclear receptor binding protein 1.2358 0.3055 0.0476 up ASL Argininosuccinate lyase 1.2144 0.2803 0.0013 up SORBS1 Sorbin and SH3 domain-containing protein 0.8223 -0.2821 0.049 down Loc317456 Hypothetical LOC317456 0.8260 -0.2863 0.00198 down Scfd1 Sec1 family domain-containing protein 1 0.819 -0.2878 0.049 down Fundc1 FUN14 domain-containing protein 1 0.8176 -0.2905 0.0399 down Mtmr4 Myotubularin-related protein 4 0.8177 -0.2903 0.0436 down Marcks11 MARCKS-related protein 0.8167 -0.2919 0.0356 down Gsta1 Glutathione S-transferase 1 0.8130 -0.2985 0.0021 down Cma1 Chymase 1 0.8115 -0.3014 0.0071 down Zfp777 Similar to KIAA1285 protein 0.8007 -0.3206 0.0011 down PNK-Beta-subunit Phosphorylase b kinase regulatory subunit 0.8225 -0.3231 0.0166 down Vps33b Vacuolar protein sorting-associated protein 33B 0.7910 -0.3382 0.0444 down Dpp9 Dipeptidyl peptidase 9 0.7788 -0.3423 0.0372 down Myh2 Myosin heavy chain 2 0.7901 -0.3560 0.005 down Pccb Propionyl-CoA carboxylase beta chain 0.7716 -0.3734 0.023 down Exoc2 Exocyst complex component 2 0.7689 -0.3791 0.0151 down Szrd1 SUZ domain-containing protein 1 0.7648 -03869 0.0230 down MLIP Muscular LMNA-interacting protein 0.7639 -0.3884 0.0288 down Rpap3 RNA polymerase II-associated protein 3 0.7628 -0.3907 0.0155 down Hsbp1 Heat shock factor-binding protein 1 0.7809 -0.3923 0.0415 down Arhgef12 Rho guanine nucleotide exchange factor 12 0.7542 -0.4070 0.0346 down Txlng Similar to CXORF15 0.7434 -0.4277 0.0198 down Trappc9 Trafficking protein particle complex 9 0.7352 -0.4436 0.0377 down Sf1 Splicing factor 1 0.7258 -0.4623 0.0178 down Myl2 Myosin regulatory light chain 2 0.7227 -0.4684 0.048 down Kcnq1 Potassium voltage-gated channel subfamily KQT member 1 0.7171 -0.4798 0.0388 down Apoa4 Apolipoprotein A-IV 0.7029 -0.5086 0.0036 down Mt1m Metallothionein 0.7022 -0.5100 0.0480 down Ptpn2 Tyrosine-protein phosphatase non-receptor type 2 0.6787 -0.5592 0.0248 down Nppb Natriuretic peptides B 0.7665 -0.5616 0.0451 down Nmt2 Glycylpeptide N-tetradecanoyltransferase 0.6196 -0.6906 0.0329 down 3.3. GO Functional Annotation and Enrichment Analysis In the biological process (BP) (Figure3)category, differential proteins in the model group were involved in cardiac muscle hypertrophy，striated muscle hypertrophy，muscle hypertrophy，muscle process. In the cellular component (CC) category, proteins belonged to the anatomical entity of the cell, including intracellular，cytoplasm，organelle envelope，outer membrane. In the molecular function (MF) category, most of them had a binding function, while others had catalytic activity. The hypergeometric test was used to analyze the functional classification or pathway in which differentially represented proteins were significantly enriched compared with the background proteins (the total number of proteins with quantitative and annotated information) (P ≤ 0.05). 3.4. KEEG Functional Annotation and Enrichment Analysis To better understand the functions of the identified differential proteins in physiological or pathological activities and to determine the metabolic and signaling pathways involved, we carried out KEEG pathway analysis for the differential proteins. Our analyses showed that the differential proteins were mainly involved in the following biological process: Adrenergic signaling in cardiomyocytes, Oxidative phosphorylation, Carbon metabolisim, Cardiac muscle contraction. The pathway with the highest KEEG enrichment was Cardiac muscle contraction. (Figure 4、5、6、7). 4. Discussion In this study, we found that UA、 CK 、 CK-MB 、TNT levels were significantly increased in hyperuricemia rats which was consistent with researchers. Emerging evidence suggests a pathogenic role of hyperuricemia in the development of hypertension and CVD, by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and may be also responsible for microvascular damage through stimulation of the renin-angiotensin system (RAS) [ 9 – 11 ]. Our study showed that 40 different proteins were found compared hyperuricemia rats with normal rats myocardial celles, 11 proteins were up-regulated and 30 proteins were down-regulated. Up-regulated proteins including CCDC88C, Lpin1, SPG11, SDHD, Rap2a, Tacc1, Cox7b, MRPS7, Erlec1, NRBP1 and ASL. Among which some proteins correlated with inflammations. Several studies suggested that [ 12 – 13 ]that (coiled-coil domain containing 88C) CCDC88C encodes a member of the hook-related proteins involved in the regulation of the Wnt signaling pathway, however, the Wnt signaling pathway controls inflammatory responses induced by multiple factors, in that study, CCDC88C expression may correlated with inflammation induced by hyperuricemia. The bioinformatic analysis allowed us to identify that LPIN1 is indentifeid to be a gene that correlated with sever inflammation[ 14 ];Recent study defined cardiac-specific roles for LPIN1 in regulating cardiac lipid levels and cardiac reserve in response to functionally demanding stimuli [ 15 – 16 ]. Mutations in vesicle-trafficking-associated SPG11, leading to loss of spatacsin function, impair the formation of membrane tubules in lysosomes and cause lysosomal lipid accumulation[ 17 ]. Resent study indicated that, circ-SPG11 was upregulated in osteoarthritis tissues and osteoarthritis model cells. Circ-SPG11 knockdown promoted the proliferation and undermined the apoptosis, inflammatory factors generation, and ECM degradation in osteoarthritis model cells[ 18 ]. Study indicated that Succinate dehydrogenase SDHD mutations may lead to protein destabilization, mitochondrial damage, reactive oxygen species(ROS)production, genomic instability, and tumor formation. SDHD also be concerned responsible for the development of hypertension.In this study, SDHD up-regulated may because of ROS induced by hyperuricemia[ 19 – 20 ]. Rap2, a member of the Rap GTP-binding proteins, plays important roles in tumorigenesis and cancer progression[ 21 – 22 ].In recent studies demonstrated that Rap2a expression is predominantly increased in renal cell carcinoma (RCC cell lines)[ 23 ], was an independent prognostic factor of worse outcome in RCC patients. Rap2A is overexpressed in a multitude of human cancers and plays an important role in cytoskeleton rearrangement, arteriogenesis and cell migration[ 24 ].In this study It may related Cellular apoptosis.Transforming, acidic coiled-coil-containing protein 1 Tacc1 also Correlated with cell apoptosis[ 25 ].Cytochrome c oxidase subunit 7B (COX7B) correlated with heart dysfunctions and LV remodeling [ 26 – 28 ].In this study, it may correlated with cardiomyocytes injury. Study speculated that alterations in 28S ribosomal protein S7 MRPS7 expression might be related to mitochondrial dysfunction .This dysfunction could be the main source of ROS following the increase in energy demands and efficient mitochondrial function-dependent excessive inflammatory activities [ 29 – 30 ], It was coordinated with our study. Argininosuccinate lyase (ASL) is tumor correlated protein which induced cell apoptosis[ 31 ]. Studied showed that ASL increased in early stage but reduced in severe stages of CKD by Using the renal ablation/infarction (A/I) injury model [ 32 – 33 ]. In our study, it may because of hyperuricemia made cell apoptosis and kidney injury . Under normal circumstance, down regulated proteins considered to be protective factors. However, in our study some proteins among them as Apolipoprotein A-IV APOA4[ 34 ] were related to mycardiol injury. Sorbin and SH3 domain-containing protein SORBS1[ 35 ] were related to cardiomyopathy hypertrophy and recent studies indicated that deletion polymorphisms in GSTA1 genes associated with overall and cardiovascular mortality as well as the death from myocardial infarction (MI) and stroke (CVI) in dialysis patients[ 36 ]. In our study, there would be kidney and cardiomycytes dameges which may regulated this protein expressions. Our study showed that there was myocardial injury in Hyperuricmia rats. Through GO functional annotation, it was found that all those protein were mostly expressions in entire cell, biological process include muscle and cardiac muscle hypertrophy and related proteins KEEG pathway mainly involved in cardiac muscle contraction. Cardiac striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity[ 37 ]. Study showed that multiple stimuli that alter cardiac contraction can drive the development of hypertrophy and myofibroblast activation. Myofibroblasts secrete large amounts of extracellular matrix, contributing to fibrosis frequently seen with cardiomyopathies [ 38 ]. Injured cardiomyocytes undergoes substantial remodelling (i.e., hypertrophy, dilation, changes in contraction characteristics, post-translational modification of various proteins, etc). In our study,high uric acid showed a major injury to rats cardiomyocytes,in the GO annotated it could be seen that rats cardiac muscle happened to be occur hypertrophy which might be has crucial adverse effect on cardiac muscle contraction.down refulations of Mlip confirmed the effectiveness[ 39 – 40 ]. 5. Conclusions In conculusion, high uric acid could cause myocardial damage in hyperuricemia rats, and several proteins may be involved in correlated process. However, there inquires further researches to confirm whether these proteins plays a role in between hyperuricemia and myocardial injury. Declarations Acknowledgements:No. Guarantor of the article :Dilidaer Xilifu, MD, PhD. Clinical trial number: not applicable. Funding:This study was supported by the “Tianshan Young Talent” Youth Program Project of Xinjiang Uygur Autonomous Region, China (Grant No.TSYC202301B075). Declarations Ethics approval and consent to participate: All animal procedures involved in this experiment were formally reviewed and approved by the Animal Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (Approval No. 20250424-108). The two-step euthanasia protocol of "deep anesthesia followed by physical euthanasia" adopted in this study strictly complies with the requirements for humane endpoints outlined in the Guidance on the Humane Treatment of Laboratory Animals issued by the Ministry of Science and Technology of China and the national standard *GB/T 35892-2018 Guidelines for the Ethical Review of Laboratory Animal Welfare*. Consent for publication: All authors agree with the content and the publication of the manuscript. Competing interests: The authors declare no competing interests. Data availability: I and the co-authors confirm that all data generated or analyzed during this study are included in this published article and can also be accessed under reasonable conditions. However, detailed datasets and individual data points are available from the corresponding author on reasonable request. Further, the data in our article is publicly available for the first time, which is generated and analyzed based on our experiment. And our submission above is not associated with any other published article at this time. References HONG F, ZHENG A, XU P, et al. High-Protein Diet Induces Hyperuricemia in a New Animal Model for Studying Human Gout [J]. Int J Mol Sci, 2020, 21(6). HE H, GUO P, HE J, et al. Prevalence of hyperuricemia and the population attributable fraction of modifiable risk factors: Evidence from a general population cohort in China [J]. Front Public Health, 2022, 10: 936717. RAO J, YE P, LU J, et al. 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Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 06 Jan, 2026 Editor assigned by journal 05 Jan, 2026 Editor invited by journal 15 Dec, 2025 Submission checks completed at journal 13 Dec, 2025 First submitted to journal 13 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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1","display":"","copyAsset":false,"role":"figure","size":212331,"visible":true,"origin":"","legend":"\u003cp\u003eEach point in the figure represents a protein, the abscissa represents the multiple change of each protein compared with control group(take the logarithm with the base of 2), the ordinate represents the P-VALUE of the student's T-test (take the negative logarithm with the base of 10), the color of the scatter represents the final screening results, the significantly up-regulated differential expression protein is shown in red, the significantly down-regulated differential expression protein is shown in blue, and gray represent no statistical difference.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/9c256027b2290173e0f14741.png"},{"id":99775343,"identity":"0209dfef-d51f-4511-bcce-00c92a8cda09","added_by":"auto","created_at":"2026-01-08 09:50:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":394427,"visible":true,"origin":"","legend":"\u003cp\u003ePoint size in the figure represents LOG_ FOLDCHANGE value. The larger the point is, the larger the corresponding LOG_ FOLDCHANGE value is; The color of the dots represents the up and down points of the difference proteins compared with control group，the line represents the value of the correlation coefficient of the corresponding location protein, and the redder the color is, the stronger the correlation is.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/ea873a107ca38f2d309dab8b.png"},{"id":100356444,"identity":"94fad6be-9fd7-492c-8751-e6816dfc3f42","added_by":"auto","created_at":"2026-01-16 07:09:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":224009,"visible":true,"origin":"","legend":"\u003cp\u003eThe abscissa is GO Term, the ordinate is the number of mapped differential expression proteins, red represents BP annotation information, green represents CC annotation information, blue represents MF annotation information, and transparency represents the size of the pvalue. The darker the color, the smaller the pvalue.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/08c1c21e26e5de885aa4152a.png"},{"id":99797625,"identity":"8a97102e-5c0c-4e73-8ecb-a7f174a54dd9","added_by":"auto","created_at":"2026-01-08 13:46:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":280890,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/f636bc801a93248eb60a1a77.png"},{"id":99775334,"identity":"1c21e46b-effc-4bba-a8c7-bf4148cc1bac","added_by":"auto","created_at":"2026-01-08 09:50:58","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":561314,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/285348437cd5330b2478ef5b.png"},{"id":99798945,"identity":"4d77a84a-3f69-412c-8789-e0d5a7a82cc7","added_by":"auto","created_at":"2026-01-08 13:49:03","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":169188,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/eb2c97e41ab5ea8e53a1244a.png"},{"id":99799114,"identity":"509676db-1df5-4c11-8206-6f1753e9c408","added_by":"auto","created_at":"2026-01-08 13:49:14","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":75489,"visible":true,"origin":"","legend":"\u003cp\u003eThe abscissa in the figure is pvalue, and the ordinate is the path name. The column length indicates the size of the pvalue. The smaller the column length, the smaller the pvalue; The redder the color, the more differentially expressed proteins mapped to this pathway..\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/9b30e8286e5f9dbf871b3065.png"},{"id":99797943,"identity":"0b5115f3-80d7-43cd-b769-a51a0b11b52e","added_by":"auto","created_at":"2026-01-08 13:46:56","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":87408,"visible":true,"origin":"","legend":"\u003cp\u003eUnnumbered image in Results \u0026nbsp;section.\u0026nbsp;\u003c/p\u003e","description":"","filename":"UNUNMBERED.png","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/e3caaba4ae26ad164844a8e3.png"},{"id":100376403,"identity":"92db6ad7-d24d-469b-8d83-13e44042fbc0","added_by":"auto","created_at":"2026-01-16 08:44:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2262301,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8268831/v1/a6272a63-8e61-44fd-9db2-b35f35589c65.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Proteomic Analysis on Myocardial Injury Induced by Hyperuricemia Rats","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn recent years, studies showed that Genetic and environmental factors combined contributed to the development of hyperuricemia and gout [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Hyperuricemia has been associated with many diseases such as cardiovascular diseases, stroke, chronic kidney disease, and hypertension [\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Is there any definite gene correlated between hyperuricemia and cardiovascular disease still be not clear. In this study, we aimed to determine whether any gene protein in high uric cid related to myocardial injury and to identify the molecular pathways implicated in this process. For this, we used yeast extract powder (YEP) and oxonic acid potassium salt (OA) establish a hyperuricemia rat model. Monitering uric acid (UA) and Troponin (TNT), observing myocardial cells pathological changes compared and using TMT-based quantitative proteomics to identificated differential proteins of cardiomyocyte in hyperuricemia rats, analyzed GO functional and KEEG functional to determined these proteins irrelated pathway.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e2.1.\u0026nbsp;Animals\u003c/p\u003e\n\u003cp\u003eTwenty-four male Sprague-Dawley (SD) rats, weighing 203.8 \u0026plusmn; 32.15 g, were provided by the Animal Experiment Center (SPF-grade) of Xinjiang Medical University. All animals were acclimatized for one week before the experiment, with body weight measured twice weekly for drug dosage adjustment. The animals were bred and maintained in the institutional animal center under standard conditions (12 h light/dark cycle, 22 \u0026plusmn; 2 \u0026deg;C, 50\u0026ndash;60% humidity), with ad libitum access to food and water.\u0026nbsp;The animals used in this study were uniformly bred and supplied by the institutional animal center, and did not in-volve privately owned or farm-sourced animals; therefore, obtaining owner consent was not applicable.\u003c/p\u003e\n\u003cp\u003e2.2.\u0026nbsp;Drug intervention\u003c/p\u003e\n\u003cp\u003eA total of 24 male SD rats were randomly divided into 2 groups (12 rats/group). To establish hyperuricemia models, rats were intragastrically administered YEP (production batch no. 20090705; Beijing Aoboxing Biological Technology Co, Ltd, Beijing, China,mixed with standard feed at a proportion of 1:4), and intraperitoneally injected with 200 mg/kg/day OA (production batch no. 20120312; Sigma‐Aldrich Co, Munich,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGermany).\u003c/p\u003e\n\u003cp\u003e2.3.\u0026nbsp;Specimen collection\u003c/p\u003e\n\u003cp\u003eBlood samples (2 ml) were collected in the morning at 0, 2, and 4 weeks. Prior to blood collection via orbital sinus/plexus puncture (a common method often referred to as \u0026ldquo;retro-orbital bleeding\u0026rdquo;), rats were briefly anesthetized by inhalation of isoflurane to ensure humane handling and eliminate procedural pain. A standard induction chamber was used with 4\u0026ndash;5% isoflurane in oxygen (flow rate: 1\u0026ndash;2 L/min) for rapid induction (within 2\u0026ndash;3 minutes). Once the righting reflex was lost, the rat was quickly transferred, and anesthesia was maintained at a surgical plane using a nose cone delivering 2\u0026ndash;3% isoflurane. The entire blood collection procedure was completed within 1\u0026ndash;2 minutes per animal to minimize anesthesia duration and physiological stress. This inhalation anesthesia protocol is widely adopted in rodent studies for brief invasive procedures and aligns with established guidelines for laboratory animal welfare. Following collection, blood samples were allowed to clot naturally and then centrifuged at 1509.3 \u0026times; g for 15 min (Allegra 64R, Beckmann Coulter, Miami, FL, USA). The separated plasma was aliquoted and stored at \u0026minus;80\u0026deg;C until analysis for UA and TnT levels.\u003c/p\u003e\n\u003cp\u003e2.4.\u0026nbsp;HE\u0026nbsp;staining\u003c/p\u003e\n\u003cp\u003eAfter successful fixation of myocardial tissue, 25px needs to be trimmed ✖️ 25px ✖️ 5px, put it into the embedding box, rinse with running water (remove the fixative in the tissue) for 30 minutes. As for the dehydration of alcohol with different concentrations, the alcohol with low concentration to high concentration is generally used as the dehydrating agent to gradually remove the water in the tissue block. Then put the tissue block in the transparent agent xylene which is soluble in both alcohol and paraffin for transparency, and replace the medium alcohol of the tissue block with xylene, then the tissue block can be immersed in wax for embedding.\u003c/p\u003e\n\u003cp\u003ePut the transparent tissue block in the melted paraffin and put it into the wax dissolving box for heat preservation. After the paraffin is completely immersed in the tissue block, it is embedded, cooled and solidified into blocks. Only when the embedded tissue blocks become hard can they be cut into very thin sections on the microtome. Fix the embedded wax block on the slicer and cut it into thin slices, generally 5-8 microns thick. The cut slices are often wrinkled. They should be put into heated water for ironing, and then pasted onto the glass slides. They should be dried in a 45 ℃ constant temperature oven, dewaxed, watered, and dyed.\u003c/p\u003e\n\u003cp\u003e2.5.\u0026nbsp;Ultrastructure of myocardial celles\u003c/p\u003e\n\u003cp\u003eAfter the pancreatic tissue added with electron microscope fixative was fixed for 2-4 hours, it was rinsed 3 times with 0.1M phosphate buffer PB (PH7.4) for 15 minutes each time. After that, 1% osmic acid was used to fix it at room temperature of 20 ℃ for 2 hours, and 0.1M phosphate buffer PB (PH7.4) was used to rinse it for 3 times, each time for 15 minutes. After that, the pancreatic tissue was dehydrated with 50% - 70% - 80% 90% - 95% alcohol for 15 minutes each time. Penetrate with acetone 812 embedding agent=1:1 for 2-4 hours, acetone: 812 embedding agent=2:1 overnight, pour the pure 812 embedding agent into the embedding plate 5-8 hours later, insert the sample into the embedding plate, then put it in the 37 ℃ oven overnight, and then polymerize it in the 60 ℃ oven for 48 hours. Pancreatic tissue block or tissue slice shall be cut thin enough (no more than 80 nm). After sectioning, use uranium lead double staining (2% uranium acetate saturated alcohol solution, lead citrate, each staining for 15 minutes) to dry the section interpretation overnight. Finally, observe under fluoroscopy electron microscope and collect images for analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.6.\u0026nbsp;Protein extraction\u003c/p\u003e\n\u003cp\u003eThe Myocardial tissue sample was added with liquid nitrogen for grinding, and the frozen powder was transferred to the EP tube.Add 1.0mL lysate into the sample powder, and lyse it with ultrasonic for 10min on ice. Ultrasonic condition: pulse on 5s; pulse off 15s; power 180W ；Preparation of cracking solution buffer: 7M urea, 4% SDS, 30mM HEPES, 1mM PMSF, 2mM EDTA, 10mM DTT, 1X protease inhibitor.After ultrasound, centrifugate 10000g at 4 ℃ for 30 minutes, and take the supernatant and protein was quantified by using BCA method.100\u0026mu;g protein solution of each sample is transferred to a new EP tube, and 100mM triethylammonium bicarbonate (TEAB) is added to it up to 100 \u0026mu;l. Add DTT to the final concentration to10mM. 55 ℃ water bath for 1h. After removal, add IAA rapidly to the final concentration to 35mM, and left the dark room for 1h.\u003c/p\u003e\n\u003cp\u003eAdd more than 4 times volume of sample solution with precooled acetone, and precipitate at - 20 ℃ for more than 3h. Centrifuge in 4 ℃, 20000g, 30min, and take the sediment.Add 1ml of 50% acetone and 50% of ethanol solution to suspend and precipitate, and precipitate at - 20 ℃ for more than 3h. Centrifuge, 4 degrees, 20000g, 30min, and take the sediment. and this step was repeated twice. Then Add 100 \u0026micro; L 100mM TEAB solution for mixing.\u003c/p\u003e\n\u003cp\u003e2.7.\u0026nbsp;Proteolysis\u003c/p\u003e\n\u003cp\u003eProtein precipitation adding 100 \u0026mu; L 100mM TEAB, 1 \u0026micro; g/\u0026micro; l of Trypsin, and to per 100ug of protein substrate add 1.0 \u0026micro;g of enzyme, soaked in 37℃water at 37 for 4h, and then add 1.0 \u0026micro; g of Trypsin，soaked in 37℃water at 37 for.Centrifuge 5000g solution to the bottom of EP tube.Peptide solution was dried into powder by freeze dryer，then take 1 \u0026micro; g enzymolysis sample from each sample to 1h LC-MS analysis.\u003c/p\u003e\n\u003cp\u003e2.8.\u0026nbsp;Peptide labeling\u003c/p\u003e\n\u003cp\u003eAfter the peptide solution iwas freeze-dried, add 100 \u0026mu; L 50mM TEAB solution to dissolution.TMT10 labeling reagent was balanced to room temperature.Add 41 \u0026micro; L acetonitrile into each tube of labeling reagent, vortex it for 1 min, and centrifuge it to the bottom of the tube.The labeling reagents are added to the corresponding peptide solution according to the labeling information table, and different samples are labeled with isotopes of different sizes.After the peptide segment was mixed with the labeling reagent, it is thrown to the bottom of the tube and left at room temperature for 2h.1 ug of each sample was mixed for labeling efficiency test.Mix the marked samples into one sample and transfer it to a new EP tube.Freeze and dried the labeled sample.\u003c/p\u003e\n\u003cp\u003e2.9.\u0026nbsp;Desalination of TMT labeled peptide\u003c/p\u003e\n\u003cp\u003eUse 400 \u0026micro; L 0.1% TFA, 0.5% acetonitrile solution to dissolve the dried mixed labeled peptide.Use 200 \u0026micro; L 0.1% TFA and 60% acetonitrile to activate the desalting column.Use 400-600 \u0026micro; L 0.1% TFA, 1% acetonitrile solution to balance the desalination columnAdd the redissolved sample into the desalting column, the labeled peptide was captured by the desalting column, and other non hydrophobic small molecules such as salt flow out and discard.Add 200 \u0026micro; L 0.1% TFA and 0.5% acetonitrile solution to clean the desalting column and remove residual salts. Add 300 \u0026micro; L 0.1% TFA, 60% acetonitrile solution, make the liquid flow slowly through the desalting column, elute the peptide segment, and use a new EP tube to collect the elution solution.Freeze end dried the eluting solution to remove acetonitrile.\u003c/p\u003e\n\u003cp\u003e2.10.\u0026nbsp;Separation of TMT labeled Peptides by High pH Reversed Phase Liquid Chromatography\u003c/p\u003e\n\u003cp\u003eHigh pH mobile phase A was 10mM ammonium formate, pH=10.0 (adjusted by chromatographic pure ammonia); High pH mobile phase B was 10mM ammonium formate[7], 90% acetonitrile, pH=10.0 (adjusted by chromatographic pure ammonia).The TMT labeled peptide powder was desalted with 52 \u0026micro; L A-phase solvent. Ultra high performance chromatographic column (BEH C18 1.7 \u0026micro; m, 2.1 \u0026times; 150mm). The flow rate is 250 \u0026micro; L/min, and the ultraviolet detection is at 215 nm.From 2 minutes, collect 1 tube every 1.0 minutes. According to the chromatographic peak type, the fractions are combined into 12 fractions.\u003c/p\u003e\n\u003cp\u003e2.11.\u0026nbsp;Mass Spectrum detection\u003c/p\u003e\n\u003cp\u003eThe spray voltage of the ion source was 2.3kv, the heating capillary of Orbitrap fusion mass spectrometer was set at 320 ℃, and the data dependent mode was adopted to automatically switch between MS and MS / MS for acquisition. The full scan MS uses Orbitrap to perform the first scanning. The scanning range is m/z 400-1600, and the resolution was set to 120000 (m/z 200 places). The maximum ion introduction time is 50ms, the Automatic gain control (AGC) is set to 1x106, and then in 3 seconds, the parent ions that meet the cascade (MS/MS) fragmentation conditions were broken by using High energy C-trap dissociation (HCD) and scanned with orbitrap, with the scanning resolution set to 15000. The scanning range is automatically controlled according to the mass charge ratio of the parent ion. The minimum scanning range is fixed at m/z=110, and the maximum scanning range was 2000. The minimum ion strength value for MS/MS is set to 50000, and the scanning resolution is 30000. In MS/MS, the maximum ion introduction time was 80ms, the AGC control was set to 1.0x105, and the parent ion selection window was set to 1.6 Dalton. MS/MS collection was carried out for ions with 2, 3 and 4 charges. The dynamic exclusion iwas set to conduct MS/MS once in 10 seconds for each parent ion, and then exclude 35% of the collision energy in 30 seconds.After inputting the mass spectrum data into Proteome Discoverer software (PD) (version 2.4.0.305, thermo Fisher Scientific), the software first screens the mass spectrum.Qualitative and quantitative database searchThe spectrogram extracted by Proteome Discoverer is searched by the Sequest HT search engine. After the search, PD software conducts quantitative analysis according to the search results and the spectrogram screened in the first step.\u003c/p\u003e\n\u003cp\u003eUniprotKB database (species Rattus norvegicus (Rat), 2021-07-25, Total entries 36153; reviewed entries 8106; unreviewed entries 28047。Database link: https://www.uniprot.org/taxonomy/10116 False positive rate of peptide and protein in search results FDR\u0026lt;1%.Differential protein was screened by the ratio and P value. Screening criteria: if fold change \u0026ge; 1.2 and P \u0026le; 0.05, then the protein was over-represented; if P \u0026le; 0.05, then the protein and fold change \u0026le; 0.833 was under-represented [8]. After pretreatment, 4744 detection proteins were retained.\u003c/p\u003e\n\u003cp\u003e2.12.\u0026nbsp;Statistical analysis\u003c/p\u003e\n\u003cp\u003eAll experimental data are expressed the mean \u0026plusmn; standard deviation (SD), The student\u0026lsquo;s t- test was used to compare categorical variables between the two groups. statistical analysis was performed with the SPSS software version 26.0. P\u0026lt;0.05 was considered to indicat a statistically significant difference.\u003c/p\u003e\n\u003cp\u003e2.13. Anesthesia and Euthanasia Protocol\u003c/p\u003e\n\u003cp\u003eAll rats were euthanized upon completion of the 4-week hyperuricemia modeling experiment to collect myocardial tissue for subsequent proteomic analysis. Prior to euthanasia, the animals were deeply anesthetized via intraperitoneal injection of pentobarbital sodium (60 mg/kg). The depth of anesthesia was confirmed by the loss of corneal and pedal withdrawal reflexes. After the animals had fully lost consciousness (approximately 5\u0026ndash;10 minutes post-injection), euthanasia was performed by cervical dislocation.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e3.1. The changes of serumUA,CK,CK-MB and TnT indexes in two groups of animal\u003c/p\u003e\n\u003cp\u003eAfter 4 weeks of pharmacological .intervention, serum UA levels in the model group \u0026nbsp;were significantly elevated compared to the control group, with a statistically significant difference (P \u0026lt; 0.05). Concurrently, serum levels of CK, CK-MB, and TnT in the model group were also markedly increased, demonstrating statistically significant differences compared to the control group (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTable1\u0026nbsp;\u003c/strong\u003eThe \u003cem\u003echanges\u003c/em\u003e of \u003cem\u003eserum UA,CK,CK-MB and TnT indexes in two groups of animal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e（x\u0026plusmn;s）\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"81%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 25px;\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 20px;\"\u003e\n \u003cp\u003e0week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 20px;\"\u003e\n \u003cp\u003e4week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 8px;\"\u003e\n \u003cp\u003et value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 9px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003cp\u003e（\u003cem\u003en\u003c/em\u003e =12）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003emodel（\u003cem\u003en\u003c/em\u003e=12）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003et value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003cp\u003e（\u003cem\u003en\u003c/em\u003e =12）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003emodel\u003c/p\u003e\n \u003cp\u003e（\u003cem\u003en\u003c/em\u003e =12）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eUric acid（UA,\u0026micro;mol/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e41.63\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e4.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e42.47\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e4.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.761\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e42.28\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e6.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e469.28\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e62.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e16.756\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003csup\u003eaa\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eCreatine Kinase（CK,U/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e87.53\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e45.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e104.66\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e53.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.595\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e116.05\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e47.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e900.83\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e423.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e4.515\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eCreatine Kinase Isoforms(CK-MB, U/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e18.47\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e4.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e13.03\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e4.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e2.128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e15.82\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e7.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e365.83\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e74.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e11.407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003csup\u003eaa\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eTroponinT(TnT,ug/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.009\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.009\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.794\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.008\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e1.316\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e0.370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e8.669\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003csup\u003eaa\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eModel group vs control group \u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＜0.05；\u003csup\u003eaa\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＜0.01\u003c/p\u003e\n\u003cp\u003e3.2 Proteomics Analysis\u003c/p\u003e\n\u003cp\u003eThe reliability of identified proteins was mainly derived from mass spectrometry (MS) analysis. The 4744 proteins were found in both the control and the treated group. Of the 4744 proteins, 4704 proteins were detected in both groups. Compared to control group，in model group the proteomic landscape reveals 11 upregulated proteins and 30 downregulated proteins (Fig. 1,2;Table 3). upregulated proteins including inflammation related protein, myocardial injury related protein and gout related protein.\u003c/p\u003e\n\u003cp\u003eTable 3 Differential Protein Information\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eProtein name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eProtein discription\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003eFC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eLog2FC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003estate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eCCDC88C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eCoiled-coil domain-containing 88C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.5736\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.6540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eLpin1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eLipin 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.3566\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.4399\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eSpg11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSPG11 vesicle-trafficking-associated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.3347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.4165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eSDHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSuccinate dehydrogenase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.3005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.3791\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eRap2a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eRAS related protein 2a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.2942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.3721\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eTacc1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eTransforming, acidic coiled-coil-containing protein 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.2503\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.3228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eCox7b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eCytochrome c oxidase subunit 7B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.3005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.3211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eMRPS7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003e28S ribosomal protein S7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.2444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.3154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eErlec1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eEndoplasmic reticulum lectin 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.2406\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.3108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eNRBP1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eNuclear receptor binding protein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.2358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.3055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0476\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eASL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eArgininosuccinate lyase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.2144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.2803\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eup\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eSORBS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSorbin and SH3 domain-containing protein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.2821\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eLoc317456\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eHypothetical LOC317456\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.2863\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.00198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eScfd1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSec1 family domain-containing protein 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.819\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.2878\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eFundc1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eFUN14 domain-containing protein 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.2905\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0399\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eMtmr4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eMyotubularin-related protein 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.2903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0436\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eMarcks11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eMARCKS-related protein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.2919\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eGsta1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eGlutathione S-transferase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.2985\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eCma1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eChymase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eZfp777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSimilar to KIAA1285 protein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003ePNK-Beta-subunit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003ePhosphorylase b kinase regulatory subunit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.8225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eVps33b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eVacuolar protein sorting-associated protein 33B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3382\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eDpp9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eDipeptidyl peptidase 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0372\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eMyh2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eMyosin heavy chain 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7901\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3560\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003ePccb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003ePropionyl-CoA carboxylase beta chain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7716\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3734\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eExoc2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eExocyst complex component 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7689\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3791\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0151\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eSzrd1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSUZ domain-containing protein 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7648\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-03869\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eMLIP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eMuscular LMNA-interacting protein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7639\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3884\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eRpap3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eRNA polymerase II-associated protein 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7628\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3907\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eHsbp1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eHeat shock factor-binding protein 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7809\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.3923\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0415\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eArhgef12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eRho guanine nucleotide exchange factor 12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.4070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eTxlng\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSimilar to CXORF15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7434\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.4277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eTrappc9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eTrafficking protein particle complex 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.4436\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eSf1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eSplicing factor 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.4623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eMyl2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eMyosin regulatory light chain 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.4684\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eKcnq1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003ePotassium voltage-gated channel subfamily KQT member 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.4798\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eApoa4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eApolipoprotein A-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.5086\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eMt1m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eMetallothionein\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.5100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003ePtpn2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eTyrosine-protein phosphatase non-receptor type 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.6787\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.5592\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eNppb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eNatriuretic peptides B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.7665\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.5616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eNmt2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 197px;\"\u003e\n \u003cp\u003eGlycylpeptide N-tetradecanoyltransferase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.6196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-0.6906\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.0329\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003edown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e3.3.\u0026nbsp;GO Functional Annotation and Enrichment Analysis\u003c/p\u003e\n\u003cp\u003eIn the biological process (BP) (Figure3)category, differential proteins in the model group were involved in cardiac muscle hypertrophy，striated muscle hypertrophy，muscle hypertrophy，muscle process. In the cellular component (CC) category, proteins belonged to the anatomical entity of the cell, including intracellular，cytoplasm，organelle envelope，outer membrane. In the molecular function (MF) category, most of them had a binding function, while others had catalytic activity. The hypergeometric test was used to analyze the functional classification or pathway in which differentially represented proteins were significantly enriched compared with the background proteins (the total number of proteins with quantitative and annotated information) (P \u0026le; 0.05).\u003c/p\u003e\n\u003cp\u003e3.4. KEEG Functional Annotation and Enrichment Analysis\u003c/p\u003e\n\u003cp\u003eTo better understand the functions of the identified differential proteins in physiological or pathological activities and to determine the metabolic and signaling pathways involved, we carried out KEEG pathway analysis for the differential proteins. Our analyses showed that the differential proteins were mainly involved in the following biological process: Adrenergic signaling in cardiomyocytes, Oxidative phosphorylation, Carbon metabolisim, Cardiac muscle contraction. The pathway with the highest KEEG enrichment was Cardiac muscle contraction. (Figure 4、5、6、7).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn this study, we found that UA、\u003cem\u003eCK\u003c/em\u003e、\u003cem\u003eCK-MB\u003c/em\u003e、TNT levels were significantly increased in hyperuricemia rats which was consistent with researchers. Emerging evidence suggests a pathogenic role of hyperuricemia in the development of hypertension and CVD, by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and may be also responsible for microvascular damage through stimulation of the renin-angiotensin system (RAS) [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study showed that 40 different proteins were found compared hyperuricemia rats with normal rats myocardial celles, 11 proteins were up-regulated and 30 proteins were down-regulated. Up-regulated proteins including CCDC88C, Lpin1, SPG11, SDHD, Rap2a, Tacc1, Cox7b, MRPS7, Erlec1, NRBP1 and ASL.\u003c/p\u003e \u003cp\u003eAmong which some proteins correlated with inflammations.\u003c/p\u003e \u003cp\u003eSeveral studies suggested that [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]that (coiled-coil domain containing 88C) CCDC88C encodes a member of the hook-related proteins involved in the regulation of the Wnt signaling pathway, however, the Wnt signaling pathway controls inflammatory responses induced by multiple factors, in that study, CCDC88C expression may correlated with inflammation induced by hyperuricemia. The bioinformatic analysis allowed us to identify that LPIN1 is indentifeid to be a gene that correlated with sever inflammation[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e];Recent study defined cardiac-specific roles for LPIN1 in regulating cardiac lipid levels and cardiac reserve in response to functionally demanding stimuli [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Mutations in vesicle-trafficking-associated SPG11, leading to loss of spatacsin function, impair the formation of membrane tubules in lysosomes and cause lysosomal lipid accumulation[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Resent study indicated that, circ-SPG11 was upregulated in osteoarthritis tissues and osteoarthritis model cells. Circ-SPG11 knockdown promoted the proliferation and undermined the apoptosis, inflammatory factors generation, and ECM degradation in osteoarthritis model cells[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Study indicated that Succinate dehydrogenase SDHD mutations may lead to protein destabilization, mitochondrial damage, reactive oxygen species(ROS)production, genomic instability, and tumor formation. SDHD also be concerned responsible for the development of hypertension.In this study, SDHD up-regulated may because of ROS induced by hyperuricemia[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Rap2, a member of the Rap GTP-binding proteins, plays important roles in tumorigenesis and cancer progression[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].In recent studies demonstrated that Rap2a expression is predominantly increased in renal cell carcinoma (RCC cell lines)[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], was an independent prognostic factor of worse outcome in RCC patients. Rap2A is overexpressed in a multitude of human cancers and plays an important role in cytoskeleton rearrangement, arteriogenesis and cell migration[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].In this study It may related Cellular apoptosis.Transforming, acidic coiled-coil-containing protein 1 Tacc1 also Correlated with cell apoptosis[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].Cytochrome c oxidase subunit 7B (COX7B) correlated with heart dysfunctions and LV remodeling [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].In this study, it may correlated with cardiomyocytes injury. Study speculated that alterations in 28S ribosomal protein S7 MRPS7 expression might be related to mitochondrial dysfunction .This dysfunction could be the main source of ROS following the increase in energy demands and efficient mitochondrial function-dependent excessive inflammatory activities [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], It was coordinated with our study. Argininosuccinate lyase (ASL) is tumor correlated protein which induced cell apoptosis[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Studied showed that ASL increased in early stage but reduced in severe stages of CKD by Using the renal ablation/infarction (A/I) injury model [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In our study, it may because of hyperuricemia made cell apoptosis and kidney injury .\u003c/p\u003e \u003cp\u003eUnder normal circumstance, down regulated proteins considered to be protective factors. However, in our study some proteins among them as Apolipoprotein A-IV APOA4[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] were related to mycardiol injury. Sorbin and SH3 domain-containing protein SORBS1[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] were related to cardiomyopathy hypertrophy and recent studies indicated that deletion polymorphisms in GSTA1 genes associated with overall and cardiovascular mortality as well as the death from myocardial infarction (MI) and stroke (CVI) in dialysis patients[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In our study, there would be kidney and cardiomycytes dameges which may regulated this protein expressions.\u003c/p\u003e \u003cp\u003eOur study showed that there was myocardial injury in Hyperuricmia rats. Through GO functional annotation, it was found that all those protein were mostly expressions in entire cell, biological process include muscle and cardiac muscle hypertrophy and related proteins KEEG pathway mainly involved in cardiac muscle contraction. Cardiac striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Study showed that multiple stimuli that alter cardiac contraction can drive the development of hypertrophy and myofibroblast activation. Myofibroblasts secrete large amounts of extracellular matrix, contributing to fibrosis frequently seen with cardiomyopathies [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Injured cardiomyocytes undergoes substantial remodelling (i.e., hypertrophy, dilation, changes in contraction characteristics, post-translational modification of various proteins, etc). In our study,high uric acid showed a major injury to rats cardiomyocytes,in the GO annotated it could be seen that rats cardiac muscle happened to be occur hypertrophy which might be has crucial adverse effect on cardiac muscle contraction.down refulations of Mlip confirmed the effectiveness[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn conculusion, high uric acid could cause myocardial damage in hyperuricemia rats, and several proteins may be involved in correlated process. However, there inquires further researches to confirm whether these proteins plays a role in between hyperuricemia and myocardial injury.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements:No.\u003c/p\u003e\n\u003cp\u003eGuarantor of the article :Dilidaer Xilifu, MD, PhD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003eFunding:This study was supported by the \u0026ldquo;Tianshan Young Talent\u0026rdquo; Youth Program Project of Xinjiang Uygur Autonomous Region, China (Grant No.TSYC202301B075).\u003c/p\u003e\n\u003cp\u003eDeclarations Ethics approval and consent to participate:\u0026nbsp;All animal procedures involved in this experiment were formally reviewed and approved by the Animal Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (Approval No. 20250424-108). The two-step euthanasia protocol of \u0026quot;deep anesthesia followed by physical euthanasia\u0026quot; adopted in this study strictly complies with the requirements for humane endpoints outlined in the \u003cem\u003eGuidance on the Humane Treatment of Laboratory Animals\u003c/em\u003e issued by the Ministry of Science and Technology of China and the national standard *GB/T 35892-2018 Guidelines for the Ethical Review of Laboratory Animal Welfare*.\u003c/p\u003e\n\u003cp\u003eConsent for publication: All authors agree with the content and the publication of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eData availability: I and the co-authors confirm that all data generated or analyzed during this study are included in this published article and can also be accessed under reasonable conditions. However, detailed datasets and individual data points are available from the corresponding author on reasonable request. Further, the data in our article is publicly available for the first time, which is generated and analyzed based on our experiment. And our submission above is not associated with any other published article at this time.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHONG F, ZHENG A, XU P, et al. High-Protein Diet Induces Hyperuricemia in a New Animal Model for Studying Human Gout [J]. Int J Mol Sci, 2020, 21(6).\u003c/li\u003e\n\u003cli\u003eHE H, GUO P, HE J, et al. Prevalence of hyperuricemia and the population attributable fraction of modifiable risk factors: Evidence from a general population cohort in China [J]. Front Public Health, 2022, 10: 936717.\u003c/li\u003e\n\u003cli\u003eRAO J, YE P, LU J, et al. 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Identification of a novel muscle A-type lamin-interacting protein (MLIP) [J]. J Biol Chem, 2011, 286(22): 19702-13.\u003c/li\u003e\n\u003cli\u003eSAUCERMAN J J, TAN P M, BUCHHOLZ K S, et al. Mechanical regulation of gene expression in cardiac myocytes and fibroblasts [J]. Nat Rev Cardiol, 2019, 16(6): 361-78.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Hyperuricemia, Protein, Myocardial injury, Proteomic, Troponin","lastPublishedDoi":"10.21203/rs.3.rs-8268831/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8268831/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHyperuricemia (HUA) has been confirmed to be closely associated with the occurrence and progression of cardiovascular diseases; however, the specific molecular mechanisms through which it induces myocardial injury remain to be fully elucidated. This study aimed to investigate the cardiotoxic effects of HUA and explore associated proteomic alterations by establishing a HUA rat model. Myocardial injury was assessed by measuring serum levels of uric acid (UA), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), and cardiac troponin T (cTnT). Differential protein expression profiles were analyzed using proteomic techniques. The results showed significantly elevated levels of UA, CK, CK-MB, and cTnT in the model group. A total of 40 differentially expressed proteins were identified, including 11 up-regulated and 30 down-regulated proteins, such as CCDC88C, LPIN1, and SDHD, which are associated with inflammatory response, oxidative stress, and mitochondrial dysfunction. GO functional analysis indicated that these proteins are involved in biological processes including myocardial hypertrophy, contraction, and fibrosis. This study reveals potential mechanisms by which HUA may contribute to myocardial injury at the protein level, providing a theoretical basis for further research.\u003c/p\u003e","manuscriptTitle":"Proteomic Analysis on Myocardial Injury Induced by Hyperuricemia Rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-08 09:50:53","doi":"10.21203/rs.3.rs-8268831/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-01-06T13:08:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-05T08:19:56+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-15T05:55:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-13T18:50:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-12-13T18:44:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9eadb89c-f29d-44a0-9ea4-c63131a72ba7","owner":[],"postedDate":"January 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-08T09:50:53+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-08 09:50:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8268831","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8268831","identity":"rs-8268831","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}