PTEN-induced kinase 1 (PINK1) Mediating Mitophagy and its Correlation to Subclinical Atherosclerosis in Patients with Psoriatic Arthritis

PTEN-induced kinase 1 (PINK1) Mediating Mitophagy and its Correlation to Subclinical Atherosclerosis in Patients with Psoriatic Arthritis | 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 PTEN-induced kinase 1 (PINK1) Mediating Mitophagy and its Correlation to Subclinical Atherosclerosis in Patients with Psoriatic Arthritis Nehad Ezzat Hamza, AE El-deeb, Elham M Kassem, Amal Mohamad El-Barbary, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7204510/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Subclinical atherosclerosis is linked to elevated risks of cardiovascular disease (CVD) as well as systemic inflammation in psoriatic arthritis patients (PsA). Objectives This study aimed to measure protein kinase 1 (PINK1) in PsA patients as well as to determine its association with subclinical atherosclerosis and disease activity (DA). Methods The current case-control study involved 40 PsA patients, in addition to 40 matched control subjects. DA was evaluated via the DAPSA score, and laboratory investigations included ESR, CRP, uric acid, total lipid profile, and PINK1 levels. Ultrasound was utilized to evaluate the carotid intima-media thickness (CIMT) as well as flow-mediated dilatation (FMD) of the brachial artery (BA). Results PsA patients exhibited a marked reduction in flow-mediated dilation (FMD) compared to controls. A marked positive correlation was detected between PINK1 and DAPSA score, Total cholesterol (TC), and CIMT, while a negative correlation was observed between PINK1 and FMD. Multivariate logistic regression analysis identified the DAPSA score, TC, CIMT, and PINK1 as potential predictive factors for subclinical atherosclerosis in PsA individuals. Conclusion Subclinical atherosclerosis was evident in PsA cases. Serum PTEN-induced kinase 1 (PINK1) may serve as a useful marker of PsA activity and could be considered a promising biomarker for detecting subclinical atherosclerosis in PsA cases. Subclinical atherosclerosis carotid intima media thickness flow-mediated dilatation PTEN induced kinase1 (PINK1) psoriatic arthritis Figures Figure 1 Figure 2 Figure 3 Introduction Psoriatic arthritis (PsA) is a chronic autoinflammatory disease most frequently linked to psoriasis. Patients with PsA have elevated risks of cardiovascular morbidity and major cardiovascular events compared to healthy individuals (Aljohani 2022 ). Increasing inflammatory load correlates with a greater incidence of subclinical atherosclerosis in this population (Kluge et al. 2013 ). Atherosclerosis is defined by fibrous elements and lipid accumulation in the large arteries, initiated by endothelial dysfunction, which triggers an inflammatory response and the development of foam cells (Jebari-Benslaiman et al. 2022 ). Endothelial dysfunction is influenced by multiple factors, with mitochondrial dysfunction identified as the primary cause and a significant contributor to CVD (Kirkman et al. 2021 ). Endothelial-mitochondrial dysfunction can be detected early and may serve as a biomarker for the early CVD detection (Ajoolabady et al. 2022 ). PTEN-induced PINK1 is crucial for regulating mitochondrial quality, acting as a sensor for mitochondrial damage and initiating mitochondrial quality control (MQC) pathways in response to this impairment (Gündüz et al. 2017 ). This study aimed to examine PINK1 in PsA cases as well as to investigate its association with DA and subclinical atherosclerosis. Patients and methods The study recruited 40 PsA cases, diagnosed as per the CASPAR classification criteria for PsA (Taylor et al. 2006 ), along with 40 healthy subjects matched for sex and age, serving as the control group. These patients were recruited from the Rheumatology Department’s Outpatient Clinics at Tanta University Hospitals. All participants signed informed consent. The study was conducted in accordance with the Declaration of Helsinki and received approval from the Ethics Committee of the Faculty of Medicine, Tanta University, on June 6, 2022, with approval code 35532/6/22. Exclusion Criteria Patients with conditions that influence lipid profiles or PINK1 levels, including systemic inflammatory conditions, known cardiovascular disease, diabetes mellitus, neurodegenerative diseases, and malignancy, were excluded. Clinical Assessment All subjects received a thorough clinical examination and an assessment of their medical history. DA was evaluated utilizing the DAPSA score (Aletaha et al. 2017 ), while assessment of the physical functional abilities was conducted utilizing HAQ-DI (Borman et al. 2007 ). Laboratory investigations : Sampling Ten milliliters of venous blood samples were withdrawn from both the control group and PsA patients following a 12-hour overnight fasting period. In order to calculate the erythrocyte sedimentation rate (ESR), 1.6 mL of blood was transferred to a vacutainer tube that contained 0.4 mL of sodium citrate. The residual blood was transferred to a plain glass tube, permitted to clot at the ambient temperature, and centrifuged for ten minutes at 2000 rpm for serum separation. Assessment of C-reactive protein and the lipid profile was done immediately, along with serum aliquots kept at − 80°C for subsequent analyses. Patients and controls underwent CRP, ESR, and a complete lipid profile (TG, HDL, CHOL, and LDL), as well as TG/HDL ratio and serum PINK1 analysis utilizing the ELISA technique. Ultrasound assessment : a) Carotid intima-media thickness : The common carotid intima media thickness (CIMT) was measured using a B-mode ultrasound with a 7.5–10 MHz linear phased array transducer from Samsung Medison (UGEO H60). The common carotid arteries were examined using both transverse and longitudinal scans. CIMT was assessed at the far wall of both the left and right common carotid arteries, with measurements taken twice (on each side), a minimum of 1 cm adjacent to the carotid bifurcation. Subsequently, the mean CIMT was determined by averaging the CIMT values from both sides. CIMT can be calculated as the measurement of the distance from the lumen-intima interface leading edge to the media-adventitia interface leading edge. Plaque is characterized by focal wall thickening that exceeds fifty percent of the surrounding vessel wall or by localized intimal thickening < 1 mm that extends into the lumen. A carotid IMT more than or equal to 0.9 mm and/or atherosclerotic plaque presence was defined as subclinical atherosclerosis (Sobchak et al. 2019 ). b) Flow-mediated dilatation : A B-mode ultrasound with a linear transducer (10 MHz) was utilized for the measurement of FMD of the BA. The baseline diameter of the BA (Di) was measured, followed by the induction of brachial ischemia through inflation of a pneumatic cuff positioned above the antecubital fossa to a pressure 50 mmHg above the systolic arterial blood pressure. After a 5-minute interval, the pneumatic cuff was deflated, and the BA diameter (Df) was assessed from a longitudinal image captured 60 seconds followig deflation. FMD of the BA was calculated utilizing the formula, FMD = [(Df - Di) / Di] × 100 (Mućka et al. 2022 ). Statistical analysis The data were analyzed utilizing statistical measures including median, percentages, mean, range, standard deviation (SD), median, and frequencies (number of cases), as appropriate. The Kruskal-Wallis test was utilized to compare numerical variables across the study groups. Two-sided p-values below 0.05 were deemed statistically significant. Statistical analyses were conducted utilizing IBM SPSS software (IBM Corp-Armonk-NY-USA), version 22. A P-value of less than 0.05 was deemed significant. Results The demographic, clinical and laboratory data of PsA patients are shown in Table 1 . There was markedly diminished FMD in PsA patients compared to the controls. However, a substantial increase was observed in ESR, CRP, uric acid, lipid profile (TC, TG, LDL, and TG/HDL), and PINK1 concentration in PsA cases compared to controls. No marked differences were detected between the groups in terms of age and sex distribution. Regarding to Function grades and activity scores, the mean HAQ-DI score was 1.72 ± 0.27with 14(35%) had mild score, 23(57.5%) had moderate score and 3(7.5%) had severe score, while the mean DAPSA score was 22.69 ± 2.58 with 10(25%) had high score, 21(52.5%) had moderate score and 9 (22.5%) had mild score, respectively. There was a marked positive correlation between PINK1 and DAPSA scores in PsA patients, as well as between PINK1 and TC, and between PINK1 and CIMT. A negative correlation was also noted between PINK1 and FMD of the BA in PsA cases (Table 2 ). The multivariable linear regression analysis showed that CIMT, DAPSA, TC, and PINK1 concentration could be used as significant predictive factors for subclinical atherosclerosis in PsA patients (Table 3 ). In Fig. 1, there is increased CIMT by ultrasound in a PsA patient measuring 0.9 mm (Fig. 1), and in Figs. 2 and 3, there is a sonographic imaging of the same patient showing brachial artery diameter at rest DI = 0.46 (Fig. 2), and after occlusion DF = 0.48 (Fig. 3) with the resultant FMD% in this case = 4.3%. Discussion Atherosclerosis initiates with endothelial dysfunction, influenced by multiple factors, with mitochondrial dysfunction identified as the primary cause and a key contributor to CVD (Kirkman et al. 2021 ). This study investigated PINK1 role, a biomarker of mitophagy, in subclinical atherosclerosis among PsA patients and its correlation with DA. This study's findings indicate a notable rise in LDL, TG, TC, and TG/HDL levels within the PsA case group, supporting the research of Pietrzak et al. ( 2019 )d jcik et al. (2019), who concluded that among patients with psoriasis and PsA, there was altered lipid metabolism. Our results regarding CIMT and FMD showed markedly elevated CIMT and substantially decreased FMD, indicating the presence of early subclinical atherosclerosis in PsA cases. This is in agreement with Gündüz et al. ( 2023 ), who found that CIMT was significantly elevated in PsA cases compared with healthy controls. Babalic et al. ( 2022 ) also illustrated that FMD at the BA was diminished in PsA patients compared to controls. The results of our study showed markedly elevated PINK1 concentration in PsA patients, which correlates with disease activity. This finding aligns with that of Nam et al. ( 2022 ), who reported that PINK1 expression was increased in the synovial membranes of RA patients at ( p < 0.0001) compared to controls. Cossu et al. ( 2021 ) also investigated 24 Japanese multiple sclerosis (MS) patients and observed that CSF and PINK1 serum concentrations were upregulated in those with MS compared to controls. They attributed this finding to the hyperactivation of inflammatory signaling pathways and subsequent chronic systemic inflammation, resulting from impaired mitochondrial energy metabolism. This impairment led to Ca 2+ homeostasis loss, elevated reactive oxygen species (ROS), and apoptotic cell death. Another study by Eltokhy et al. ( 2022 ) examined 60 atopic bronchial asthma children and found that PARK and PINK-1 mRNA expressions were substantially elevated due to chronic inflammation and ROS overproduction during allergic attacks. This study revealed a positive correlation between PINK1 and TC, CIMT, alongside a negative correlation between PINK1 and FMD. This finding is significant as it indicates a potential function of PINK1 in the early detection of subclinical atherosclerosis, an area that has not been thoroughly explored and may offer a new perspective on PsA. This aligns with the findings of Ajoolabady et al. ( 2022 ), who demonstrated that in a therosclerosis murine model, increased PINK1-PRKN mitophagy leads to accelerated proliferation and exacerbation of atherosclerotic lesions in vascular smooth muscle cell. Wang et al. (2021) further demonstrated that excessive activation of the PINK1-PRKN mitophagy pathway in obese murine hearts paradoxically mediates cardiac injury. They also found that suppression of PINK1 and inhibition of excessive mitophagy alleviate obesity-induced cardiac disorders in H9c2 cells and in vivo mouse models. The multivariable linear regression analysis to evaluate the factors associated with subclinical atherosclerosis in PsA patients revealed that PINK1 concentration, in addition to CIMT, TC, and DAPSA, was a positive predictor of subclinical atherosclerosis in PsA patients. This finding aligns with multiple systematic reviews examining the prevalence and presence of subclinical atherosclerosis in PsA patients (Zhen et al. 2022; Mbaa et al. 2022 ; Sobchak et al. 2017). Overall, this research supports the significance of PINK1 as a mitophagy marker, potentially influencing the early development of atherosclerosis in PsA patients. Conclusion Subclinical atherosclerosis was evident in PsA patients. In addition, PINK1 may serve as a reliable marker for PsA activity and can be considered a promising biomarker for detecting subclinical atherosclerosis in PsA patients. Declarations Ethics approval and consent to participate: This study involving human participants were reviewed and approved by the local ethics committee of Faculty of Medicine, Tanta University, Egypt with approval code 35532/6/22 . All tests were explained to all patients before having their written informed consent to participate in our study. This study was executed according to the code of ethics of the World Medical Association (Declaration of Helsinki) and the STROBE reporting guidelines for studies on humans. Consent for Publication: Not applicable Availability of data and materials: The datasets generated and/or analyzed during the current study are not publicly available due to [privacy / ethical restrictions] but are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: No specific grant was given to this research by funding organizations in the public, private, or not-for-profit sectors. Author Contribution All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article and take responsibility for the integrity of the work. Authors 1 and4 wrote the main manuscript text. Authors 1 and 6 drafted the manuscript. Authors 2 and 3 prepared figures . Authors 4 and 5 performed acquisition, analysis, and interpretation of data. All authors read and approved the submitted version References Ajoolabady A, Chiong M, Lavandero S, et al. Mitophagy in cardiovascular diseases: molecular mechanisms, pathogenesis, and treatment. Trends Mol Med. 2022; 28:836–49. Aletaha D, Alasti F, Smolen JS. Disease activity states of the DAPSA, a psoriatic arthritis specific instrument, are valid against functional status and structural progression. Ann Rheum Dis. 2017; 76:418–21. Aljohani R. Metabolic Syndrome and Its Components in Psoriatic Arthritis. Open Access Rheumatol. 2022; 14:7–16. Babalic F.C.A, Borza C., Ilie Rosca C., et al. Caraba Endothelial dysfunction in psoriatic arthritis patients: correlations between insulin resistance and disease activity. Eur Rev Med Pharmacol Sci. 2022; 18: 6796–804. Borman P, Toy GG, Babaoğlu S, et al. Comparative evaluation of quality of life and life satisfaction in patients with psoriatic and rheumatoid arthritis. Clin Rheumatol 2007; 26: 330–34. Cossu D, Yokoyama K, Sechi LA. Potential of PINK1 and PARKIN proteins as biomarkers for active multiple sclerosis: a Japanese cohort study. Front. Immunol 2021; 12: 681386. Eltokhy AK, Toema O, El-Deeb OS. The correlation between Pink-1/Parkin mediated mitophagy, endoplasmic reticulum stress and total polyamines in pediatric bronchial asthma: an integrated network of pathways. Mol Biol Rep. 2022; 49:227–235. Gündüz ÖS, Alptürker KA, Şen Rüb C, et al. Mitochondrial quality control by the PINK1/parkin system. Cell Tissue Res. 2017; 367:111–23. Gündüz ÖS, Alptürker KA, Şen MG. The relationship of carotid intima-media thickness with cell adhesion molecules and pentraxin-3 in patients with psoriatic arthritis. Aktuelle Rheumatol. 2023; 48: 78–85. Jebari-Benslaiman S, Galicia-García U, Larrea-Sebal A, et al. Pathophysiology of atherosclerosis. Int J Mol Sci. 2022; 23:3346. Kirkman DL, Robinson AT, Rossman MJ, et al. Mitochondrial contributions to vascular endothelial dysfunction, arterial stiffness, and cardiovascular diseases. Am J Physiol Heart Circ Physiol. 2021;320. Kluge MA, Fetterman JL, Vita JA. Mitochondria and endothelial function. Circ Res. 2013; 112:1171–88. Mbaa, B. Ppm, C. Sp. Health risk assessment of heavy metals concentration from soil; a case study of the Mayo-Dallah in Southern area of Chad. J. Radiat. Res. Appl. Sci. 2022; 15: 130–8. Mućka S, Miodońska M, Jakubiak GK, et al. Endothelial Function Assessment by Flow-Mediated Dilation Method: A Valuable Tool in the Evaluation of the Cardiovascular System. Int J Environ Res Public Health. 2022; 19:11242. Nam J-H, Lee J-H, Choi H-J. TNF-α induces mitophagy in rheumatoid arthritis synovial fibroblasts, and mitophagy inhibition alleviates synovitis in collagen antibody-induced arthritis. Int. J. Mol. Sci. 2022; 23: 5650. Pietrzak A, Chabros P, Grywalska E, et al. Serum lipid metabolism in psoriasis and psoriatic arthritis - an update. Arch Med Sci. 2019;15: 369–75. Sobchak C, Eder L. Cardiometabolic disorders in psoriatic disease. Curr Rheumatol Rep 2017; 19: 63. Sobchak C, Akhtari S, Harvey P, et al. Value of carotid ultrasound in cardiovascular risk stratification in patients with psoriatic disease. Arthritis Rheumatol 2019; 71:1651–9. Taylor W, Gladman D, Helliwell P, et al. CASPAR Study Group. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006; 54:2665–73. Wang S-H. LncRNA H19 governs mitophagy and restores mitochondrial respiration in the heart through Pink1/Parkin signaling during obesity. Cell Death Dis 2021:12; 1–16. Wójcik, Piotr, Michał Biernacki, Adam Wroński, et al. Altered Lipid Metabolism in Blood Mononuclear Cells of Psoriatic Patients Indicates Differential Changes in Psoriasis Vulgaris and Psoriatic Arthritis. Int. J. Mol. Sci. 2019; 20: 4249. Zhen He, Guoqiang Wu, Zhiyong Li. Carotid ultrasound for assessing the subclinical atherosclerosis in psoriatic arthritis patients: A propensity scores matching analysis. J. Radiat. Res. Appl. Sci..2022; 15:4. Tables Table 1. Demographic, clinical and laboratory findings of patients and controls. Variables Patients (N = 40) Mean± SD Controls (N = 40) Mean± SD p value Age (years) 41.21±10.04 33.89±9.39 0.061 Sex: Males No (%) Females No (%) 3 (7.5%) 37 (92.5%) 1 (2.5%) 39 (97.5%) 0.30 Duration of PSA (years) 10.75± 3.5 ESR (mm/h) 35.87±9.5 8.75±2.5 0.001* CRP (mg/l) 7.55± 3.5 3.28± 0.7 0.001* Serum uric acid (mg/dl) 4.79±1.85 3.19 ±0.22 0.031* TC (mg/dl) 167.53±14.57 121.67±12.25 0.0001* TG (mg/dl) 128.15± 55.5 96.76± 13.5 0.003* TG/ HDL 2.49± 8.92 1.87± 1.8 0.0032* LDL (mg/dl) 163.30±38.89 98.82±28.4 0.0001* CIMT (mm) 0.628±0.03 0.498±0.02 0.041* FMD (%) 8.3 ± 4.2 10.8 ± 2.7 0.0001* PINK1 concentration(ng/L): 1731.06± 97.3 869.63± 28.6 0.0001* ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, T . C : total cholesterol. T.G: triglyceride. HDL: high density lipoprotein. LDL: low density lipoprotein. CIMT: carotid intima-media thickness, FMD: flow-mediated dilatation of the brachial artery, PINK1: PTEN- induced kinase 1. *: Statistically significant at p ≤ 0.05 Table 2: The correlation of PINK1 concentration with demographic data, clinical and laboratory findings in the psoriatic arthritis patients. PINK1 concentration. R P-value Age (years) 0.204 0.206 Female sex 0.532 0.725 ESR 0.093 0.568 CRP 0.188 0.245 Uric acid 0.0288 0.859 HAQ N 0.2814 0.078 DAPSA 0.5125 0.0007* T.G 0.191 0.237 T.C 0.4471 0.0038* HDL-C -0.119 0 .509 LDL-C 0.224 0 .210 FMD -0.1136 0.312 CIMT 0.473 0.002* ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, HAQ: Health Assessment Questionnaire, DAPSA: Disease Activity in Psoriatic Arthritis, T.C: total cholesterol. T.G: triglyceride. HDL: high density lipoprotein, LDL: low density lipoprotein., CIMT: carotid intima-media thickness, FMD: flow-mediated dilatation of the brachial artery, PINK1: PTEN- induced kinase 1. *: Statistically significant at p ≤ 0.05 Table 3: Multivariable linear regression model of independent predictors for sub clinical atherosclerosis in patients with psoriatic arthritis. Predictors B p-value OR 95% CI Lower limit Upper limit Age 0.952 0.744 1.017 0.509 1.357 CIMT 0.323 0.045* 0.724 0.529 0.990 DAPSA 1.839 0.047* 6.290 0.944 41.895 HAQ N 0.742 0.402 0.805 0.578 1.358 FMD 0.016 0.062 1.011 0.981 1.037 PINK1concentration 1.542 0.008* 2.83 1.30 5.82 ESR -0.035 0.891 0.965 0.584 1.596 CRP 1.457 0.064 4.568 0.648 21.498 Uric acid 0.024 0.447 0.975 0.879 1.032 T.C 0.023 0.046* 1.072 0.958 1.091 T.G 1.843 0.248 2.842 1.368 5.753 HDL-C 0.033 0.435 0.679 0.783 0.965 LDL-C 0.161 0.626 0.851 0.739 0.981 ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, HAQ: Health Assessment Questionnaire, DAPSA: Disease Activity in Psoriatic Arthritis, T.C: total cholesterol. T.G: triglyceride. HDL: high density lipoprotein. LDL: low density lipoprotein. CIMT: carotid intima-media thickness, FMD: flow-mediated dilatation of the brachial artery, PINK1: PTEN- induced kinase 1. *: Statistically significant at p ≤ 0.05, B: Regression coefficient, OR: odds ratio, CI: Confidence interval, *p<0.05 is statistically significant. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7204510","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":500639269,"identity":"b53028ea-df0f-451f-afd6-62df63be4021","order_by":0,"name":"Nehad Ezzat Hamza","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"Nehad","middleName":"Ezzat","lastName":"Hamza","suffix":""},{"id":500639270,"identity":"446cf161-a5fa-44ba-a41c-693f093fdab3","order_by":1,"name":"AE El-deeb","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"AE","middleName":"","lastName":"El-deeb","suffix":""},{"id":500639271,"identity":"0aa07701-7167-4474-b1e2-a0912178bfa5","order_by":2,"name":"Elham M Kassem","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"Elham","middleName":"M","lastName":"Kassem","suffix":""},{"id":500639272,"identity":"8152be70-1266-49a6-bb3e-afe40c53d6ce","order_by":3,"name":"Amal Mohamad El-Barbary","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"Amal","middleName":"Mohamad","lastName":"El-Barbary","suffix":""},{"id":500639273,"identity":"f368409b-629b-4f05-88c5-926876d22e24","order_by":4,"name":"Rasha A. Gaber","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"Rasha","middleName":"A.","lastName":"Gaber","suffix":""},{"id":500639274,"identity":"a48d36d8-7611-462e-be65-7863abca2a7e","order_by":5,"name":"Rehab Mahmoud Salem","email":"data:image/png;base64,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","orcid":"","institution":"Tanta University","correspondingAuthor":true,"prefix":"","firstName":"Rehab","middleName":"Mahmoud","lastName":"Salem","suffix":""}],"badges":[],"createdAt":"2025-07-24 10:23:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7204510/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7204510/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89657738,"identity":"51d6f430-bbc7-49d3-98af-81bbdd3e6b9e","added_by":"auto","created_at":"2025-08-22 10:37:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":204617,"visible":true,"origin":"","legend":"\u003cp\u003eA sonographic imaging of female patient aged 47 years old with PsA showing CIMT = 0.9 mm.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7204510/v1/706059aa2f8ea6a919106276.png"},{"id":89656413,"identity":"4e0d08a8-bc1d-4f1b-820f-22bcd507e6e2","added_by":"auto","created_at":"2025-08-22 10:29:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":167966,"visible":true,"origin":"","legend":"\u003cp\u003eA sonographic imaging for the same patient showing brachial artery diameter at rest (DI) =0.46cm.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7204510/v1/f3c80b2d4c9c9399bd40aa9d.png"},{"id":89656417,"identity":"ad21efae-92ca-4f5d-873d-3eeb94d6950d","added_by":"auto","created_at":"2025-08-22 10:29:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":156918,"visible":true,"origin":"","legend":"\u003cp\u003eA sonographic imaging for the same patient showing brachial artery diameter after occlusion (DF) =0.48 cm.\u003c/p\u003e\n\u003cp\u003eFMD % = ((DF-Di)/DI) x 100 = 4.3 %.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7204510/v1/ff8023379c5f0a74eb1142a7.png"},{"id":92323168,"identity":"150d9aac-36e5-4406-82aa-3185afa43ecb","added_by":"auto","created_at":"2025-09-27 16:31:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1563160,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7204510/v1/d71e75b6-fdc1-41e0-aee7-6b10530d4533.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"PTEN-induced kinase 1 (PINK1) Mediating Mitophagy and its Correlation to Subclinical Atherosclerosis in Patients with Psoriatic Arthritis","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePsoriatic arthritis (PsA) is a chronic autoinflammatory disease most frequently linked to psoriasis. Patients with PsA have elevated risks of cardiovascular morbidity and major cardiovascular events compared to healthy individuals (Aljohani \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIncreasing inflammatory load correlates with a greater incidence of subclinical atherosclerosis in this population (Kluge et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Atherosclerosis is defined by fibrous elements and lipid accumulation in the large arteries, initiated by endothelial dysfunction, which triggers an inflammatory response and the development of foam cells (Jebari-Benslaiman et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eEndothelial dysfunction is influenced by multiple factors, with mitochondrial dysfunction identified as the primary cause and a significant contributor to CVD (Kirkman et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Endothelial-mitochondrial dysfunction can be detected early and may serve as a biomarker for the early CVD detection (Ajoolabady et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). PTEN-induced PINK1 is crucial for regulating mitochondrial quality, acting as a sensor for mitochondrial damage and initiating mitochondrial quality control (MQC) pathways in response to this impairment (G\u0026uuml;nd\u0026uuml;z et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). This study aimed to examine PINK1 in PsA cases as well as to investigate its association with DA and subclinical atherosclerosis.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003eThe study recruited 40 PsA cases, diagnosed as per the CASPAR classification criteria for PsA (Taylor et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2006\u003c/span\u003e), along with 40 healthy subjects matched for sex and age, serving as the control group. These patients were recruited from the Rheumatology Department\u0026rsquo;s Outpatient Clinics at Tanta University Hospitals. All participants signed informed consent.\u003c/p\u003e\u003cp\u003e The study was conducted in accordance with the Declaration of Helsinki and received approval from the Ethics Committee of the Faculty of Medicine, Tanta University, on June 6, 2022, with approval code 35532/6/22.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eExclusion Criteria\u003c/strong\u003e\u003cp\u003ePatients with conditions that influence lipid profiles or PINK1 levels, including systemic inflammatory conditions, known cardiovascular disease, diabetes mellitus, neurodegenerative diseases, and malignancy, were excluded.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eClinical Assessment\u003c/strong\u003e\u003cp\u003eAll subjects received a thorough clinical examination and an assessment of their medical history. DA was evaluated utilizing the DAPSA score (Aletaha et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), while assessment of the physical functional abilities was conducted utilizing HAQ-DI (Borman et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2007\u003c/span\u003e).\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLaboratory investigations\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSampling\u003c/strong\u003e\u003cp\u003eTen milliliters of venous blood samples were withdrawn from both the control group and PsA patients following a 12-hour overnight fasting period. In order to calculate the erythrocyte sedimentation rate (ESR), 1.6 mL of blood was transferred to a vacutainer tube that contained 0.4 mL of sodium citrate. The residual blood was transferred to a plain glass tube, permitted to clot at the ambient temperature, and centrifuged for ten minutes at 2000 rpm for serum separation. Assessment of C-reactive protein and the lipid profile was done immediately, along with serum aliquots kept at \u0026minus;\u0026thinsp;80\u0026deg;C for subsequent analyses.\u003c/p\u003e\u003c/p\u003e\u003cp\u003ePatients and controls underwent CRP, ESR, and a complete lipid profile (TG, HDL, CHOL, and LDL), as well as TG/HDL ratio and serum PINK1 analysis utilizing the ELISA technique.\u003c/p\u003e\u003cp\u003e\u003cb\u003eUltrasound assessment\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ea) Carotid intima-media thickness\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe common carotid intima media thickness (CIMT) was measured using a B-mode ultrasound with a 7.5\u0026ndash;10 MHz linear phased array transducer from Samsung Medison (UGEO H60). The common carotid arteries were examined using both transverse and longitudinal scans. CIMT was assessed at the far wall of both the left and right common carotid arteries, with measurements taken twice (on each side), a minimum of 1 cm adjacent to the carotid bifurcation. Subsequently, the mean CIMT was determined by averaging the CIMT values from both sides. CIMT can be calculated as the measurement of the distance from the lumen-intima interface leading edge to the media-adventitia interface leading edge. Plaque is characterized by focal wall thickening that exceeds fifty percent of the surrounding vessel wall or by localized intimal thickening\u0026thinsp;\u0026lt;\u0026thinsp;1 mm that extends into the lumen. A carotid IMT more than or equal to 0.9 mm and/or atherosclerotic plaque presence was defined as subclinical atherosclerosis (Sobchak et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eb) Flow-mediated dilatation\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eA B-mode ultrasound with a linear transducer (10 MHz) was utilized for the measurement of FMD of the BA. The baseline diameter of the BA (Di) was measured, followed by the induction of brachial ischemia through inflation of a pneumatic cuff positioned above the antecubital fossa to a pressure 50 mmHg above the systolic arterial blood pressure. After a 5-minute interval, the pneumatic cuff was deflated, and the BA diameter (Df) was assessed from a longitudinal image captured 60 seconds followig deflation. FMD of the BA was calculated utilizing the formula, FMD = [(Df - Di) / Di] \u0026times; 100 (Mućka et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003cp\u003eThe data were analyzed utilizing statistical measures including median, percentages, mean, range, standard deviation (SD), median, and frequencies (number of cases), as appropriate. The Kruskal-Wallis test was utilized to compare numerical variables across the study groups. Two-sided p-values below 0.05 were deemed statistically significant. Statistical analyses were conducted utilizing IBM SPSS software (IBM Corp-Armonk-NY-USA), version 22. A P-value of less than 0.05 was deemed significant.\u003c/p\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe demographic, clinical and laboratory data of PsA patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There was markedly diminished FMD in PsA patients compared to the controls. However, a substantial increase was observed in ESR, CRP, uric acid, lipid profile (TC, TG, LDL, and TG/HDL), and PINK1 concentration in PsA cases compared to controls. No marked differences were detected between the groups in terms of age and sex distribution. Regarding to Function grades and activity scores, the mean HAQ-DI score was 1.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27with 14(35%) had mild score, 23(57.5%) had moderate score and 3(7.5%) had severe score, while the mean DAPSA score was 22.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.58 with 10(25%) had high score, 21(52.5%) had moderate score and 9 (22.5%) had mild score, respectively.\u003c/p\u003e\u003cp\u003eThere was a marked positive correlation between PINK1 and DAPSA scores in PsA patients, as well as between PINK1 and TC, and between PINK1 and CIMT. A negative correlation was also noted between PINK1 and FMD of the BA in PsA cases (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The multivariable linear regression analysis showed that CIMT, DAPSA, TC, and PINK1 concentration could be used as significant predictive factors for subclinical atherosclerosis in PsA patients (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn Fig.\u0026nbsp;1, there is increased CIMT by ultrasound in a PsA patient measuring 0.9 mm (Fig.\u0026nbsp;1), and in Figs.\u0026nbsp;2 and 3, there is a sonographic imaging of the same patient showing brachial artery diameter at rest DI\u0026thinsp;=\u0026thinsp;0.46 (Fig.\u0026nbsp;2), and after occlusion DF\u0026thinsp;=\u0026thinsp;0.48 (Fig.\u0026nbsp;3) with the resultant FMD% in this case\u0026thinsp;=\u0026thinsp;4.3%.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAtherosclerosis initiates with endothelial dysfunction, influenced by multiple factors, with mitochondrial dysfunction identified as the primary cause and a key contributor to CVD (Kirkman et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). This study investigated PINK1 role, a biomarker of mitophagy, in subclinical atherosclerosis among PsA patients and its correlation with DA.\u003c/p\u003e\u003cp\u003eThis study's findings indicate a notable rise in LDL, TG, TC, and TG/HDL levels within the PsA case group, supporting the research of Pietrzak et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2019\u003c/span\u003e)d jcik et al. (2019), who concluded that among patients with psoriasis and PsA, there was altered lipid metabolism.\u003c/p\u003e\u003cp\u003eOur results regarding CIMT and FMD showed markedly elevated CIMT and substantially decreased FMD, indicating the presence of early subclinical atherosclerosis in PsA cases. This is in agreement with G\u0026uuml;nd\u0026uuml;z et al. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), who found that CIMT was significantly elevated in PsA cases compared with healthy controls. Babalic et al. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) also illustrated that FMD at the BA was diminished in PsA patients compared to controls. The results of our study showed markedly elevated PINK1 concentration in PsA patients, which correlates with disease activity. This finding aligns with that of Nam et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), who reported that PINK1 expression was increased in the synovial membranes of RA patients at (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) compared to controls. Cossu et al. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) also investigated 24 Japanese multiple sclerosis (MS) patients and observed that CSF and PINK1 serum concentrations were upregulated in those with MS compared to controls. They attributed this finding to the hyperactivation of inflammatory signaling pathways and subsequent chronic systemic inflammation, resulting from impaired mitochondrial energy metabolism. This impairment led to Ca\u003csup\u003e2+\u003c/sup\u003e homeostasis loss, elevated reactive oxygen species (ROS), and apoptotic cell death.\u003c/p\u003e\u003cp\u003eAnother study by Eltokhy et al. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) examined 60 atopic bronchial asthma children and found that PARK and PINK-1 mRNA expressions were substantially elevated due to chronic inflammation and ROS overproduction during allergic attacks. This study revealed a positive correlation between PINK1 and TC, CIMT, alongside a negative correlation between PINK1 and FMD. This finding is significant as it indicates a potential function of PINK1 in the early detection of subclinical atherosclerosis, an area that has not been thoroughly explored and may offer a new perspective on PsA. This aligns with the findings of Ajoolabady et al. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), who demonstrated that in a therosclerosis murine model, increased PINK1-PRKN mitophagy leads to accelerated proliferation and exacerbation of atherosclerotic lesions in vascular smooth muscle cell. Wang et al. (2021) further demonstrated that excessive activation of the PINK1-PRKN mitophagy pathway in obese murine hearts paradoxically mediates cardiac injury. They also found that suppression of PINK1 and inhibition of excessive mitophagy alleviate obesity-induced cardiac disorders in H9c2 cells and in vivo mouse models. The multivariable linear regression analysis to evaluate the factors associated with subclinical atherosclerosis in PsA patients revealed that PINK1 concentration, in addition to CIMT, TC, and DAPSA, was a positive predictor of subclinical atherosclerosis in PsA patients. This finding aligns with multiple systematic reviews examining the prevalence and presence of subclinical atherosclerosis in PsA patients (Zhen et al. 2022; Mbaa et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Sobchak et al. 2017).\u003c/p\u003e\u003cp\u003eOverall, this research supports the significance of PINK1 as a mitophagy marker, potentially influencing the early development of atherosclerosis in PsA patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSubclinical atherosclerosis was evident in PsA patients. In addition, PINK1 may serve as a reliable marker for PsA activity and can be considered a promising biomarker for detecting subclinical atherosclerosis in PsA patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study involving human participants were reviewed and approved by the local ethics committee of Faculty of Medicine, Tanta University, Egypt with \u003cstrong\u003eapproval code\u0026nbsp;\u003c/strong\u003e35532/6/22\u003cstrong\u003e.\u003c/strong\u003e All tests were explained to all patients before having their written informed consent to participate in our study.\u0026nbsp;This study was executed according to the code of ethics of the World Medical Association (Declaration of Helsinki) and the STROBE reporting guidelines for studies on humans.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to [privacy / ethical restrictions] but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo specific grant was given to this research by funding organizations in the public, private, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article and take responsibility for the integrity of the work. Authors 1 and4 wrote the main manuscript text. Authors 1 and 6 drafted the manuscript. Authors 2 and 3 prepared figures . Authors 4 and 5 performed acquisition, analysis, and interpretation of data. All authors read and approved the submitted version\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAjoolabady A, Chiong M, Lavandero S, et al. Mitophagy in cardiovascular diseases: molecular mechanisms, pathogenesis, and treatment. Trends Mol Med. 2022; 28:836\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAletaha D, Alasti F, Smolen JS. Disease activity states of the DAPSA, a psoriatic arthritis specific instrument, are valid against functional status and structural progression. Ann Rheum Dis. 2017; 76:418\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAljohani R. Metabolic Syndrome and Its Components in Psoriatic Arthritis. 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Arthritis Rheumatol 2019; 71:1651\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTaylor W, Gladman D, Helliwell P, et al. CASPAR Study Group. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006; 54:2665\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang S-H. LncRNA H19 governs mitophagy and restores mitochondrial respiration in the heart through Pink1/Parkin signaling during obesity. Cell Death Dis 2021:12; 1\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eW\u0026oacute;jcik, Piotr, Michał Biernacki, Adam Wroński, et al. Altered Lipid Metabolism in Blood Mononuclear Cells of Psoriatic Patients Indicates Differential Changes in Psoriasis Vulgaris and Psoriatic Arthritis. Int. J. Mol. Sci. 2019; 20: 4249.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhen He, Guoqiang Wu, Zhiyong Li. Carotid ultrasound for assessing the subclinical atherosclerosis in psoriatic arthritis patients: A propensity scores matching analysis. J. Radiat. Res. Appl. Sci..2022; 15:4.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;Demographic, clinical and laboratory findings of patients and controls.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003ePatients (N\u0026nbsp;=\u0026nbsp;40)\u003c/p\u003e\n \u003cp\u003eMean\u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003eControls (N\u0026nbsp;=\u0026nbsp;40)\u003c/p\u003e\n \u003cp\u003eMean\u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003ep\u0026nbsp;value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e41.21\u0026plusmn;10.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e33.89\u0026plusmn;9.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex:\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMales No (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFemales No (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (7.5%)\u003c/p\u003e\n \u003cp\u003e37 (92.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (2.5%)\u003c/p\u003e\n \u003cp\u003e39 (97.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of PSA (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e10.75\u0026plusmn; 3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eESR (mm/h)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e35.87\u0026plusmn;9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e8.75\u0026plusmn;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP (mg/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e7.55\u0026plusmn; 3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e3.28\u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum uric acid (mg/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e4.79\u0026plusmn;1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e3.19 \u0026plusmn;0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.031*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTC (mg/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e167.53\u0026plusmn;14.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e121.67\u0026plusmn;12.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTG (mg/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e128.15\u0026plusmn; 55.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e96.76\u0026plusmn; 13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.003*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTG/ HDL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e2.49\u0026plusmn; 8.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e1.87\u0026plusmn; 1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.0032*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL (mg/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e163.30\u0026plusmn;38.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e98.82\u0026plusmn;28.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCIMT (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e0.628\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e0.498\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.041*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFMD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e8.3 \u0026plusmn; 4.2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e10.8 \u0026plusmn; \u0026nbsp;2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 224px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePINK1 concentration(ng/L):\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e1731.06\u0026plusmn; 97.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e869.63\u0026plusmn; 28.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eESR: erythrocyte sedimentation rate, CRP: C-reactive protein, T\u003cstrong\u003e.\u003c/strong\u003eC\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003etotal cholesterol. T.G: triglyceride. HDL: high density lipoprotein. LDL: low density lipoprotein. CIMT: carotid intima-media thickness, FMD: flow-mediated dilatation of the brachial artery, PINK1: PTEN- induced kinase 1. *: Statistically significant at p \u0026le; 0.05\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: The correlation of PINK1 concentration with demographic data, clinical and laboratory findings in the psoriatic arthritis patients.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"98%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePINK1 concentration.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale sex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.532\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.725\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eESR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.568\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.188\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.245\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUric acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.0288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.859\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHAQ N\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.2814\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDAPSA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.5125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.0007*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT.G\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.237\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT.C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.4471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.0038*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDL-C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e-0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0\u0026nbsp;.509\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL-C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0\u0026nbsp;.210\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFMD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e-0.1136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCIMT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e0.473\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eESR: erythrocyte sedimentation rate, CRP: C-reactive protein, HAQ: Health Assessment Questionnaire, DAPSA: Disease Activity in Psoriatic Arthritis, T.C: total cholesterol. T.G: triglyceride. HDL: high density lipoprotein, LDL: low density lipoprotein., CIMT: carotid intima-media thickness, FMD: flow-mediated dilatation of the brachial artery, PINK1: PTEN- induced kinase 1. *: Statistically significant at p \u0026le; 0.05\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Multivariable linear regression model of independent predictors for sub clinical atherosclerosis in patients with psoriatic arthritis.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePredictors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower limit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper limit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.952\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.744\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.509\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.357\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCIMT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.323\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.045*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.724\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.529\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDAPSA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.047*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e6.290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.944\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e41.895\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHAQ N\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.742\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.402\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.805\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.578\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.358\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFMD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.981\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.037\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePINK1concentration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.008*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e2.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e5.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eESR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e-0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.965\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.584\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.596\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.457\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e4.568\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.648\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e21.498\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUric acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.447\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.975\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.879\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.032\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT.C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.046*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.958\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.091\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT.G\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e2.842\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e1.368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e5.753\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDL-C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.435\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.679\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.783\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.965\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL-C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.626\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.851\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.739\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e0.981\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eESR: erythrocyte sedimentation rate, CRP: C-reactive protein, HAQ: Health Assessment Questionnaire, DAPSA: Disease Activity in Psoriatic Arthritis, T.C: total cholesterol. T.G: triglyceride. HDL: high density lipoprotein. LDL: low density lipoprotein. CIMT: carotid intima-media thickness, FMD: flow-mediated dilatation of the brachial artery, PINK1: PTEN- induced kinase 1. *: Statistically significant at p \u0026le; 0.05, B: Regression coefficient, OR: odds ratio, \u0026nbsp;CI: Confidence interval, *p\u0026lt;0.05 is statistically significant.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Subclinical atherosclerosis, carotid intima media thickness, flow-mediated dilatation, PTEN induced kinase1 (PINK1), psoriatic arthritis","lastPublishedDoi":"10.21203/rs.3.rs-7204510/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7204510/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSubclinical atherosclerosis is linked to elevated risks of cardiovascular disease (CVD) as well as systemic inflammation in psoriatic arthritis patients (PsA).\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e\u003cp\u003eThis study aimed to measure protein kinase 1 (PINK1) in PsA patients as well as to determine its association with subclinical atherosclerosis and disease activity (DA).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe current case-control study involved 40 PsA patients, in addition to 40 matched control subjects. DA was evaluated via the DAPSA score, and laboratory investigations included ESR, CRP, uric acid, total lipid profile, and PINK1 levels. Ultrasound was utilized to evaluate the carotid intima-media thickness (CIMT) as well as flow-mediated dilatation (FMD) of the brachial artery (BA).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003ePsA patients exhibited a marked reduction in flow-mediated dilation (FMD) compared to controls. A marked positive correlation was detected between PINK1 and DAPSA score, Total cholesterol (TC), and CIMT, while a negative correlation was observed between PINK1 and FMD. Multivariate logistic regression analysis identified the DAPSA score, TC, CIMT, and PINK1 as potential predictive factors for subclinical atherosclerosis in PsA individuals.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eSubclinical atherosclerosis was evident in PsA cases. Serum PTEN-induced kinase 1 (PINK1) may serve as a useful marker of PsA activity and could be considered a promising biomarker for detecting subclinical atherosclerosis in PsA cases.\u003c/p\u003e","manuscriptTitle":"PTEN-induced kinase 1 (PINK1) Mediating Mitophagy and its Correlation to Subclinical Atherosclerosis in Patients with Psoriatic Arthritis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-22 10:29:19","doi":"10.21203/rs.3.rs-7204510/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"48532dec-2176-4dfb-917f-a8338b05c84c","owner":[],"postedDate":"August 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-27T16:23:39+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-22 10:29:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7204510","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7204510","identity":"rs-7204510","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}