{"paper_id":"70ceab90-1b9e-4a62-864b-8b9560cf1c49","body_text":"ANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nExploring the Link between Chronic Inflammation \nand Atherosclerosis-Endometriosis Association \n \nAnastasia V. Poznyak 1,*, Vasily N. Sukhorukov 2, Igor A. Sobenin 2, Vladimir P Ofitserov 3, Alexander L \nGolovyuk 4, Dmitriy Yu Serdyukov 5, Anton Y. Postnov 2 , Alexander N. Orekhov 2,* \n \n \nAbstract \nBackground: Atherosclerotic cardiovascular disease \n(ASCVD) and endometriosis are both inflammatory \ndiseases with significant implications for clinical practice \nand public health. Evidence Acquisition: To examine the \nclinical question regarding the relationship between \nASCVD and endometriosis, we gathered data from various \nsources, including research studies and subse quent \nreference searches of retrieved articles. Our research \nstrategies focused on identifying high -quality evidence \nthrough comprehensive study time periods and rigorous \nmethods for quality assessment and article inclusion. \nResults: Our review of the lite rature reveals significant \nfindings regarding the interplay between ASCVD and \nendometriosis. Both conditions share inflammation as a \nkey factor in their pathophysiology. Inflammation not only \ncontributes to the initiation and progression of vascular \ndamage in ASCVD but also plays a role in the development \nand persistence of endometriosis. Women with \nendometriosis demonstrate higher levels of inflammatory \nmarkers and endothelial activation. Conclusions: Based on \nthe available evidence, we conclude that there is a likely \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \ngenetic link between ASCVD and the development of \nendometriosis. Additionally, the influence of estrogen on \nASCVD varies depending on the stage of atherosclerosis. \nWhile estrogen may be protective in women with early \nartery blockages, it can pose a potential risk to those with \nestablished atherosclerosis. Clinicians should consider \nthese factors when managing patients with ASCVD and \nendometriosis to optimize care. \nKeywords: Curcumin; Natural compound; Phytotherapy; \nAtherosclerosis; Cardiovascular disease. \n \nIntroduction \nEndometriosis is a prevalent and chronic non -malignant \ngynecological condition where tissue similar to the lining of the \nuterus is found outside the uterine cavity. Due to the fact that many \ncases of endometriosis in combination with other pathologies have \nbeen identified, interest in its study has grown greatly. For example, \nbased on common pathogenetic features, one of the recent st udies \nstudied the possible coexistence of cardiovascular diseases in \npatients with endometriosis (Smolarz et al., 2021). \nAlthough endometriosis was first discovered over a century ago, \nthere is still a lack of comprehensive understanding regarding its \nunderlying causes and mechanisms. The widely accepted theory is \nSampson's theory of retrograde menstruation, which suggests t hat \nmenstrual blood flows backward into the pelvis, leading to the \ndevelopment of endometrial tissue outside the uterus. However, \nsuccessful implantation and growth of this misplaced tissue in  \n  \n \n \n \n \n \n \n \n \n \n \nSignificance | Understanding shared inflammation mechanisms in \natherosclerosis and endometriosis informs innovative interdisciplinary \ntreatments, enhancing patient care and outcomes comprehensively. \n*Correspondence.  Anastasia V. Poznyak, Institute for \nAtherosclerosis Research, Osennyaya 4-1-207, \n121609 Moscow, Russia; And Alexander N. \nOrekhov, Laboratory of Cellular and Molecular \nPathology of Cardiovascular System, Federal \nState Budgetary Scientific Institution «Petrovsky \nNational Research Centre of Surgery» (FSBSI \n\"Petrovsky NRCS\"), Abrikosovsky per., 2, \nMoscow, 119991, Russia. E-mail: \ntehhy_85@mail.ru, \nalexandernikolaevichorekhov@gmail.com \n \nEditor Aman Shah Bin Abdul Majid  And accepted by the Editorial Board \nMar 14, 2024 (received for review Jan 16, 2024) \n \nAuthor Affiliation.  \n1 Institute for Atherosclerosis Research, Osennyaya 4-1-207, 121609 Moscow, Russia.  \n2  Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Federal  \nState Budgetary Scientific Institution «Petrovsky National Research Centre of Surgery»  \n(FSBSI \"Petrovsky NRCS\"), Abrikosovsky per., 2, Moscow, 119991, Russia. \n3  Moscow Aviation Institute (National Research University), 4 Volokolamskoe Shosse,  \n125993 Moscow, Russia. \n4 Vascular Surgery Department, A. V. Vishnevsky National Medical Research Center of \nSurgery, 27 Bolshaya Serpukhovskaya Street, 117997 Moscow, Russia \n5 Department of Hospital Therapy, Kirov Military Medical Academy,  6 Academica \nLebedeva Street,  194044  St. Petersburg, Russia. \n \nPlease cite this article.  \nAnastasia V. Poznyak, Vasily N. Sukhorukov  et al. (2024).  Exploring the Link between \nChronic Inflammation and Atherosclerosis -Endometriosis Association , Journal of \nAngiotherapy, 8(3), 1-13, 9556 \n   \n2207-8843/© 2024 ANGIOTHERAPY, a publication of Eman Research, USA. \nThis is an open access article under the CC BY-NC-ND license. \n(http.//creativecommons.org/licenses/by-nc-nd/4.0/). \n(https./publishing.emanresearch.org). \n \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nectopic areas require additional changes in various biological \nprocesses, particularly the creation of a more immunotolerant \nperitoneal environment (Gruber and Mechsner, 2021). \nCurrently, endometriosis is regarded as a complex condition \ninfluenced by multiple factors, including hormones, immune \nresponses, anatomy, genetics, and the environment. For many \nyears, studies have been conducted on the \nimmunological/inflammatory features of endometriosis (Laganà et \nal., 2019).  \nIn the context of endometriosis, several key factors contribute to its \ninitiation, maintenance, and progression. These factors include the \ndegradation of the main extracellular matrix, resistance to \napoptosis, and the promotion of neoangiogenesis (Hogg et al., \n2020). \nPeritoneal macrophages have been identified as significant \ncontributors in these processes. As the main producers of cytokines \nand growth factors, they play a crucial role in promoting the ectopic \ngrowth of endometrial tissue fragments that have survived \nphagocytosis. Additionally, the reduced phagocytic capacity of \nmacrophages and the absorption of their own residues further \ncontribute to this process (Wilke et al., 2011). \nMoreover, certain mediators released by macrophages attract \nadditional inflammatory immune cells, such as neutrophils, type 17 \nT helper cells, and regulatory T cells. This influx of immune cells \nexacerbates the already excessive inflammatory microenvironme nt \nassociated with endometriosis (Kokot et al., 2021). \nIt is important to note that endometriosis is not limited solely to the \nabdominal cavity, as it is associated with a state of systemic \nsubclinical inflammation. This is supported by the elevated levels of \nserum cytokines and biomarkers, including C -reactive protein and \ncarbohydrate antigen 125. Based on extensive research, \nendometriosis is now recognized as a chronic systemic \ninflammatory disease. At the same time, local inflammation is \nconsidered the main cause of pelvic pain and infertility (Kokot et \nal., 2021). \nThe main component of inflammation that is associated with \nendometriosis is an increased oxidative process. Possibly, \nretrograde menstruation transfers a number of well -known \ninducers of oxidative stress into the abdominal cavity: erythrocytes, \nendometrial apoptotic tissue and cellular debris (in addition to \npelvic macrophages). Also, pro -oxidant and pro -inflammatory \nsubstances are hemoglobin and its toxic products: iron and heme. \nThe production of reactive oxygen species in the abdominal cavity \nmay be invo lved in inflammation, which is associated with \nendometriosis, as well as by regulating the expression of numerous \ninflammatory genes (Rudzitis-Auth et al., 2020). \nIn this review, we aim to examine the underlying mechanisms \nresponsible for the development of two specific conditions: \nendometriosis and atherosclerosis. We performed the \ncomprehensive analysis of existing literature to answer the \nquestion: what are the shared mechanisms of these two pathologies? \n \nEvidence Acquisition \nThe search strategy for our study was conducted following the \nPreferred Reporting Items for Systematic Reviews and Meta -\nAnalyses (PRISMA) guidelines. The primary objective of our search \nwas to investigate the linkage between atherosclerosis and \nendometriosis, with a focus on chronic inflammation as a common \nfactor between the two pathologies. \nCriteria for Eligibility: \n \n1. Study Characteristics: We included articles published \nfrom 2018 onwards to ensure the relevance of the research \nin the contemporary context. No language or publication \nstatus restrictions were imposed. \n2. Report Characteristics: Studies reporting on the \nassociation between atherosclerosis and endometriosis, \nwith an emphasis on chronic inflammation, were \nconsidered for eligibility. \nSelection Process: \n1. Screening: Initially, we conducted a preliminary search \nutilizing the PubMed database, using the keywords \n\"atherosclerosis\" and \"endometriosis\" in various \ncombinations with the Boolean operator \"AND.\" The \nsearch was limited to papers published from 2018 \nonwards. The search results were imported into a \nreference management software for further analysis. \n2. Eligibility: In the second stage, we expanded our search to \ninclude additional sources by incorporating a search in \nGoogle Scholar. We introduced the keyword \n\"inflammation,\" with or without the term \"chronic,\" and \ncombined it with the two initial keywords,  \n\"atherosclerosis\" and \"endometriosis.\" \n \nElectronic Search Strategy (Example using PubMed): \n((atherosclerosis [Title/Abstract]) AND (endometriosis \n[Title/Abstract])) AND (\"2018/01/01\"[Date -  Publication]: \n\"3000/12/31\"[Date - Publication]) \nThe above strategy reflects the combination of the keywords \n\"atherosclerosis\" and \"endometriosis\" and limits the search to \narticles published from January 1, 2018, to December 31, 3000. The \nBoolean operator \"AND\" ensures that both terms are present in the \nretrieved articles. \nLately, there has been growing attention to the influence of genetic \npredisposition in the onset of endometriosis. Endometriosis has \npolygenic inheritance (prevalence in relatives of the first degree \nfrom 4 to 9%). Furthermore, a variety of gene polymorphisms have \nbeen identified that govern the production of different components, \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nincluding estrogen receptors, detoxification enzymes, extracellular \nmatrix remodeling enzymes, cytokines, and immunomodulatory \nproteins. Simultaneously, it's important to note that certain \nvariations among these options could result in a more unfavorable \nprognosis and a heightened likelihood of endometriosis recurrence \n(Vassilopoulou et al., 2019). \n \nEndometriosis: epidemiology, symptoms, diagnosis, and \ntreatment \nIt has been reported that approximately 10% of women in their \nreproductive age experience endometriosis. However, the exact \nfigures remain unclear due to historical reliance on laparoscopy as \nthe primary diagnostic method and more recent implementation of \nmultimodal imaging techniques. Consequently, misdiagnosis \nremains prevalent, of ten causing significant delays in obtaining a \nproper diagnosis. Currently, endometriosis is estimated to affect \nanywhere between 5% to 50% of infertile women, 2% to 11% of \nasymptomatic women, and 5% to 21% of women experiencing \npelvic pain (Muhaidat et al., 2021). The most commonly observed \nindications and symptoms of endometriosis include dyspareunia, \ninfertility, chronic pelvic pain, and dysmenorrhea. It is worth \nnoting that asymptomatic cases may also occur. In the future, \nfatigue, decreased labor productivity, high consumption of \nanalgesics, decreased quality of life and depression are observed. \nEndometriosis, like diabetes, is expensive, the estimated annual cost \nper patient is 9,579 euros ( Missmer et al., 2021 ). This condition \npresents various phenotypes that are commonly associated with it. \nThese include ovarian endometriomas, superficial lesions on the \nperitoneum, deep infiltrating endometriosis, and extragenital \nmanifestations. The extragenital areas affecte d can involve \nperipheral nerves, as well as localizations in the rectum, diaphragm, \nand pleural regions (Guerriero et al., 2020). \nThe diagnosis of endometriosis remains complex and time -\nconsuming due to its varying degrees of severity, ranging from \nasymptomatic cases to severe conditions. The typical symptoms of \ndysmenorrhea, chronic pelvic pain, and dyspareunia are not \nspecific and can overlap with other conditions that impact the \nurinary and digestive systems ( Parasar et al., 2017 ). Based on the \nfamily history of endometriosis, during interviews with patients, \nkey signs of endometriosis can be identified, including the cyclical \nnature of pelvic pain, a weak reaction or lack of reaction to \nanalgesics, severe primary dysmenorrhea in adolescence and \ninfertility. Physical examination does not exclude endometriosis \n(Verket et al., 2019 ). Simultaneously, when examining the pelvic \norgans and rectum, it is possible to identify areas of infiltration and \nsensitivity that impact the pelvic cavity, including the vagina, \nrectovaginal septum, uterosacral ligaments, and Douglas sac, which \ncan be palpated. It is also worth noting that the effectivene ss of \nphysical examinations may be higher during menstruation. Non -\ninvasive imaging methods, such as transvaginal ultrasound and \nmagnetic resonance imaging, are considered crucial in the \ndiagnostic process. The diagnosis of endometriosis should rely on \nthorough examination, visualization, and patient interviews (Riazi \net al., 2019). Surgical intervention should be reserved for cases of \ndiagnostic uncertainty and persistent symptoms, even after optimal \ndrug therapy. Presently, available therapeutic options c onsist of \nnon-hormonal drug treatments (such as nonsteroidal anti -\ninflammatory drugs) and hormonal methods (including combined \noral contraceptives, progestins, and gonadotropin -releasing \nhormone analogues), as well as surgical interventions (both \nconservative and definitive) and assisted reproductive technologies \nfor individuals experiencing infertility associated with \nendometriosis (van Barneveld et al., 2020). \n \nCommon Pathogenesis of Chronic Inflammation \nASCVD (atherosclerotic cardiovascular disease) and endometriosis \nare both inflammatory conditions. Inflammation plays a crucial \nrole in initiating and sustaining vascular damage, as well as in the \nprogression of atherosclerosis, a major underlying process in long-\nterm cardiovascular disease (CVD). Studies have revealed that \nwomen diagnosed with endometriosis exhibit significantly higher \nlevels of T-lymphocytes and macrophages expressing interferon -g, \na proinflammatory cytokine (Taskin et al., 2019). Also, women with \nendometriosis have higher markers of endothelial inflammation \nand activation. In their study, Santanam et al. found that both \natherosclerotic plaques and peritoneal fluid of women with \nendometriosis encompasses a wide array of inflammatory \ncytokines, chemokines, and growth factors that contribute to the \nonset of localized inflammation. Furthermore, women with \nendometriosis face a heightened likelihood of experiencing \nmicrovascular dysfunction and atherosclerosis, which poses \nadditional risks ( Santanam et al., 2002 ). Dysregulation of \ninterferon-g production is the main association between \nendometriosis and atherosclerosis. As a result, women diagnosed \nwith endometriosis face an elevated risk of developing \nmicrovascular dysfunction and atherosclerosis (Li et al., 202 1). \nConsidering the significant contribution of inflammation, which \ncan be partly reversed, in arterial stiffness progression, \nincorporating inflammatory markers into the clinical evaluation of \ncardiovascular risk proves beneficial for wom en with \nendometriosis. By combining assessments of arterial stiffness and \nmeasuring inflammatory markers, noninvasive early detection of \ncardiovascular risk can be enhanced. And reducing inflammation \ncan reduce microvascular dysfunction (Mozos et al., 2017 ). In the \nmanagement of endometriosis, statins and other cholesterol -\nlowering medications exhibit positive effects and could potentially \nserve as a therapeutic intervention for women with this condition. \nNotably, metformin possesses anti -inflammatory properties, while \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nalso modulating ovarian steroid production and reducing serum \ncytokine levels. These combined effects make it a potential inhibitor \nin the progression of endometriosis (Kimber-Trojnar et al., 2022). \nAn analysis of existing reviews and studies on the efficacy and safety \nof statins in managing inflammation reveals promising results. \nStatins have been shown to exert anti -inflammatory effects by \ninhibiting the production of pro -inflammatory cytokines and \npromoting the release of anti -inflammatory mediators. These \nmechanisms suggest a potential role for statins in reducing \ninflammation in conditions such as atherosclerosis, rheumatoid \narthritis, and even some forms of cancer. However, while some \nstudies hav e demonstrated positive effects on inflammatory \nmarkers and disease progression, the overall clinical benefit of using \nstatins as anti -inflammatory agents remains a topic of debate. \nConcerns have been raised about the inconsistency of results across \nstudies, potential side effects, and the need for further research to \nestablish clear guidelines for their use in an anti -inflammatory \ncontext. \nSimilarly, the use of metformin as an anti -inflammatory agent has \nbeen an area of interest in the medical community. Metformin's \nanti-inflammatory properties are linked to its ability to modulate \nvarious signaling pathways involved in inflammation, such as  \nAMP-activated protein kinase (AMPK) and nuclear factor-kappa B \n(NF-kB) pathways. Studies have suggested that metformin may \nhave potential benefits in reducing inflammation associated with \nconditions like diabetes, obesity, and even certain cancers. \nHowever, conflicting results have been reported regarding the \nefficacy of metformin in directly targeting inflammation, with some \nstudies showing modest effects on inflammatory markers while \nothers have not observed significant changes. Additionally, \nconcerns have been raised about the optimal dosages, duration of \ntreatment, and potential side effects associated with using \nmetformin for its anti-inflammatory properties. \nOverall, while both statins and metformin show promise as \npotential therapeutic interventions for managing inflammation in \nclinical practice, the current evidence is not definitive. Further well-\ndesigned clinical trials and meta- analyses are needed to eluc idate \ntheir true efficacy, optimal dosages, safety profiles, and long- term \neffects in different patient populations. Additionally, considering \nthe complex nature of inflammation and its role in various diseases, \na personalized medicine approach may be nece ssary to determine \nwhich patients are most likely to benefit from anti -inflammatory \ntreatments with statins and metformin. Close monitoring of \npatients for potential adverse effects and regular reassessment of \ntreatment strategies based on evolving researc h findings will be \ncrucial in maximizing the benefits of these interventions while \nminimizing risks. \n \nGenetic Similarities \nIt is highly likely that there exists a genetic connection between \nASCVD (atherosclerotic cardiovascular disease) and the onset of \nendometriosis. Current research has identified various genes, \nincluding those found through Genome -Wide Association Studies \n(GWAS), Online Mendelian Inheritance in Man (OMIM), and \ndifferentially expressed (DEG) genes, that are associated with both \nendometriosis and ASCVD. These genes are involved in the vital \nvitamin B metabolic pathway, which plays a crucial role in overall \nmetabolism, genetic and environmental information processing, \ncellular processes, and human diseases. Notably, endometriosis \nshares a common genetic pathway with sleep disorders, myocardial \ninfarction, and coronary heart disease. For instance, genetic \nvariants of CDKN2CBAS located on chromosome 9 have been \nlinked to the development of both endometriosis and acute \nmyocardial infarction (Lalami, et al., 2021). \nEndothelial Nitric Oxide Synthase (eNOS) Pathway: The eNOS \ngene (NOS3) encodes the enzyme responsible for producing nitric \noxide (NO) in endothelial cells. NO is a vasodilator and anti -\ninflammatory molecule that plays a central role in maintaining \nvascular homeostasis. Variants in the NOS3 gene have been \nassociated with endothelial dysfunction and impaired NO \nproduction, which can contribute to the development of \natherosclerosis. Functional polymorphisms in NOS3 have been \nlinked to increased cardiovascular risk, highlighting the importance \nof this pathway in vascular health. \nEstrogen Receptor (ER) Signaling Pathway: Estrogen exerts its \neffects through binding to estrogen receptors, particularly ERα \n(ESR1) and ERβ (ESR2). Polymorphisms in these genes can \ninfluence estrogen sensitivity and signaling efficiency in endothelial \ncells. Genetic variations in ESR1 and ESR2 have been associated \nwith altered endothelial function, inflammation, and \natherosclerosis susceptibility. The functional significance lies in the \ndifferential responses to estrogen among individuals with distinct \ngenotypes, which can impact cardiovascular outcomes. \nInflammatory Pathways: Inflammation is a key driver of \natherosclerosis and endothelial dysfunction. Genetic \npolymorphisms in genes encoding pro -inflammatory cytokines \n(e.g., TNF-α, IL-6) and adhesion molecules (e.g., VCAM-1, ICAM-\n1) can amplify the inflammatory response within the vascular wall. \nVariants in these genes have been linked to increased risk of \natherosclerosis progression and adverse cardiovascular events. The \nfunctional significance lies in the dysregulation of inflammatory \npathways, promoting endothelial dysfunction and atherogenesis. \nLipid Metabolism Pathways: Dysregulation of lipid metabolism is a \nhallmark of atherosclerosis. Genetic variations in genes involved in \nlipid transport and metabolism, such as APOE, PCSK9, and LDLR, \nhave been implicated in the development of atherosclerotic plaques. \nMutations in these genes can affect lipid levels, leading to \naccelerated plaque formation and increased cardiovascular risk. \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nThe functional significance lies in the impact of genetic variants on \nlipid homeostasis, plaque stability, and atherosclerosis progression. \nUnderstanding the genetic pathways involved in estrogen signaling, \nendothelial dysfunction, and atherosclerosis provides insights into \nthe molecular mechanisms underlying cardiovascular disease \nsusceptibility. Personalized approaches that take into account  \ngenetic variations may offer tailored strategies for risk assessment, \nprevention, and treatment of vascular disorders. Further research \ninto these genetic pathways and their functional significance holds \npromise for precision medicine interventions target ing the \nintersection of estrogen-related pathways, endothelial function, and \natherosclerosis. \n \nEndometriosis, ASCVD, and MicroRNA Dysfunction \nThe discovery of microRNAs has opened up new avenues in \nexploring the connection between ASCVD (atherosclerotic \ncardiovascular disease) and endometriosis. microRNAs are small \nRNA molecules that do not code for proteins but play a role in \nregulating gene ex pression. They have the ability to influence \nprotein synthesis and regulate the expression of adhesion molecules \nthat are highly present in the cardiovascular system. Abnormal \nlevels of certain microRNAs have been observed in various \nconditions affecting h uman reproductive organs and processes, \nsuch as endometrioid adenocarcinoma of the endometrium, \npreeclampsia, ovarian adenocarcinoma, uterine leiomyomas, \nrepeated pregnancy loss, and endometriosis (Bjorkman and Taylor, \n2019). By further studying mitochondrial dysfunction, researchers \nand clinicians may gain deeper insight into the underlying \npathophysiology of seemingly unrelated diseases in the future. \nMicroRNAs (miRNAs) are increasingly recognized as pivotal \nregulators of gene expression and are playing important roles in the \ndevelopment of various diseases, including atherosclerosis and \nendometriosis. \nIn atherosclerosis, miRNAs have shown promise as potential \nbiomarkers due to their stability in blood and their altered \nexpression patterns in patients with cardiovascular disease. Specific \nmiRNAs, such as miR -21, miR -126, miR -155, and miR -33, have \nbeen fo und to influence processes like inflammation, lipid \nmetabolism, and endothelial dysfunction. Profiling these \natherosclerosis-associated miRNAs in blood samples could aid in \nearly disease detection, risk assessment, and monitoring disease \nprogression. \nMoreover, miRNAs are also being investigated as therapeutic \ntargets in atherosclerosis. Targeting atherosclerosis- related \nmiRNAs through antimiRs or miRNA mimics represents a novel \napproach for treating the disease. By modulating the expression of \nmiRNAs such as miR-33 or miR-126, which are involved in crucial \npathways associated with atherosclerosis development, we may \nhave the potential to stabilize plaques, reduce inflammation, and \nenhance vascular function, therefore providing new avenues for \ntherapy. \nWhen it comes to endometriosis, miRNAs have been implicated in \nits pathogenesis, a chronic gynecological disorder characterized by \nthe growth of endometrial -like tissue outside the uterus. \nDysregulation of specific miRNAs, including members of the miR-\n200 family, miR-21, and miR-145, has been linked to processes such \nas cell proliferation, inflammation, and angiogenesis in \nendometriosis. Detecting altered miRNA expression profiles in \nendometrial tissues and blood samples could have diagnostic and \nprognostic value for this condition. \nIn the realm of endometriosis therapy, manipulating miRNA levels \nis being explored as a potential therapeutic strategy. By targeting \nmiRNAs known to be oncogenic, like miR -21, or restoring the \nexpression of tumor-suppressive miRNAs such as those in the miR-\n200 family, we might be able to regulate pathways critical for the \ndevelopment and growth of endometriotic lesions. miRNA -based \ntherapies, including miRNA inhibitors or mimics, may offer novel \napproaches for managing inflammation, inhibiting angiogenesis,  \nand promoting apoptosis in endometriotic tissues. \nIn summary, miRNAs have the potential to serve as both \nbiomarkers and therapeutic targets in atherosclerosis and \nendometriosis. Understanding the roles of miRNAs in disease \npathophysiology and leveraging their diagnostic and therapeutic \npotentials is crucial for improving early detection, risk assessment, \nand personalized treatment approaches for these complex \nconditions. Advancing research into disease -specific miRNA \nsignatures and developing miRNA-based therapeutic interventions \nis essential for advancing precision medicine in the management of \natherosclerosis and endometriosis. \n \nEndometriosis and Ovarian Function \nEarly menopause is a well- known factor that increases the risk of \ncardiovascular disease (CVD). Studies have revealed that women \nexperiencing menopause at a younger age are more prone to \ndeveloping clinical cardiovascular conditions. This can be \nattributed to the decline in estrogen levels during menopause. \nEstrogen plays a crucial role in maintaining vascular health prior to \nmenopause by enhancing the release of nitric oxide in the arterial \nendothelium, which promotes vasodilation. Additionally, estrogen \ninhibits the proliferation of smooth muscle cells and regulates \nprostaglandin production ( Leuzzi et al., 2012). These beneficial \neffects are mediated by estrogen receptor (ER) isoforms, and \nreduced levels of ERα as well as ERα polymorphism are associated \nwith increased severity and risk of coronary heart disease. In \nendometriosis, overexpression of ERβ suppresses  ERα activity, \nresulting in elevated levels of cyclooxygenase -2. The increased \ncyclooxygenase-2 levels contribute to progesterone resistance, \ninflammation, hypoxia, oxidative stress, and proliferation of \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nsmooth muscle cells in blood vessels, ultimately leading to \nendothelial dysfunction and the development of CVD ( Eldafira et \nal., 2021). \n \nAssociation between Endometriosis and Early Menopause \nAccording to the results of the conducted research, a link between \nearly menopause and endometriosis was revealed. A study \nconducted in Japan followed 49,927 female nurses aged 25 years and \nolder. The results revealed that women with a history of \nendometriosis had a higher likelihood of experiencing early \nmenopause, with an odds ratio of 1.32 (95% confidence interval \n1.07-1.64) ( Thombre Kulkarni et al., 2022 ). These findings were \ncorroborated by a retrospective study conducted in the United \nKingdom involving 5,113 postmenopausal women. Further analysis \ndemonstrated that endometriosis causing infertility was \nsignificantly associated with early onset of menopause, even after \nadjusting for factors such as age, age at menarche, number of \npregnancies, body mass i ndex, smoking before menopause, and \nother causes of infertility (odds ratio 3.06; 95% confidence interval \n1.85-5.06). So, it becomes clear that endometriosis, which causes \ninfertility, further increases the risk of early menopause. The impact \nof endometrio sis and related surgeries on ovarian reserve \ncontributes partly to the observed effects ( Upson and Missmer, \n2020). Studies on hormone replacement therapy (HRT) during \nperimenopause have shown divergent results in terms of \ncardioprotection. Some studies suggest that early administration of \nestrogen therapy in menopausal women reduces the risk of \nmyocardial infarction, heart failure, or mortality (Reslan and Khalil, \n2012), without a significant increase in the risk of cancer or venous \nthrombosis. However, it is important to note that while estrogen \nmay have a cardioprotective effect in women with early \natherogenesis, it could be potentially harmful for those with existing \natherosclerosis. For women who began HRT within 10 years after \nmenopause, the risk factor for coronary heart disease was estimated \nto be 0.76 (95% confidence interval, 0.50- 1.16), with an absolute \nexcess risk of - 6 per 10,000 person -years (Iorga et al., 2017 ). \nSubsequent research involving women aged 50 to 59 years within \nthe first 10 years af ter menopause indicated a trend towards \nreduced overall mortality with HRT (with or without progestin). \nAmong postmenopausal women without pre -existing \ncardiovascular diseases, those who started HRT within 6 years after \nmenopause showed significantly slowe r progression of coronary \nartery intima thickness compared to those on placebo ( Maas et al., \n2021). The \"time hypothesis\" suggests that the cardiovascular effects \nof HRT depend on individual vascular conditions and the timing of \nHRT initiation relative to menopause. In the future, the presence of \nendometriosis in medical history may serve as a factor in screening \nfor atherosclerotic cardiovascular disease (ASCVD) and when \nconsidering the initiation of HRT during the menopausal \ntransition, given its association with an increased risk of ASCVD \n(Chapron et al., 2022). \nThe intricate relationship between estrogen signaling, endothelial \ndysfunction, and atherosclerosis involves complex molecular \nmechanisms that influence cardiovascular health. Estrogen plays a \ncrucial role in maintaining vascular homeostasis by exerting bo th \ngenomic and non- genomic effects on endothelial cells. Estrogen \nreceptors, particularly ERα and ERβ, are expressed in endothelial \ncells and contribute to the regulation of genes involved in vascular \ntone, inflammation, and oxidative stress. Estrogen prom otes the \nproduction of nitric oxide (NO) by endothelial nitric oxide synthase \n(eNOS), leading to vasodilation and inhibition of platelet \naggregation and smooth muscle cell proliferation. \nHowever, in conditions of estrogen deficiency, such as menopause \nor certain endocrine disorders, the protective effects of estrogen on \nthe endothelium are diminished. This imbalance in estrogen \nsignaling can lead to endothelial dysfunction, characterized b y \nreduced NO bioavailability, increased oxidative stress, \ninflammation, and impaired vascular repair mechanisms. \nEndothelial dysfunction sets the stage for the initiation and \nprogression of atherosclerosis, a chronic inflammatory disorder of \nthe arteries characterized by the accumulation of lipid-rich plaques. \nIn the context of atherosclerosis, the dysfunctional endothelium \nbecomes more permeable to circulating lipids, particularly low -\ndensity lipoprotein (LDL), which infiltrate the arterial wall and \nundergo modification, triggering an inflammatory response. \nInflammatory cytokines and adhesion molecules further promote \nthe recruitment of immune cells, such as macrophages, to the site \nof lipid deposition. Ultimately, this leads to the formation of \natherosclerotic plaques that may progress to unstable lesions prone \nto rupture, thrombosis, and vascular events like myocardial \ninfarction or stroke. \nThe interplay between estrogen signaling, endothelial dysfunction, \nand atherosclerosis underscores the importance of maintaining \nvascular health through the modulation of hormonal balance, \nlifestyle factors, and targeted therapies. Strategies aimed at \npreserving endothelial function, reducing inflammation, and \npromoting lipid metabolism may offer therapeutic avenues for \npreventing and managing atherosclerotic cardiovascular disease in \npopulations at risk, especially in the context of altered estrogen \nsignaling dynamics. \n \nEndometriosis and cardiovascular risk factors \nCardiovascular risk factors are becoming more prominent in their \ncorrelation with endometriosis (Mu et al., 2016). We proposed the \nscheme of association between endometriosis and atherosclerosis in \nFigure 1.  \n \nHypertension \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nIn their research, Mu et al. discovered a strong link between \nhypertension and endometriosis. They conducted a prospective \nstudy involving 116,430 nurses aged 25 to 42 years, observing them \nfor 20 years. Out of the participants, 4244 women were diagnosed \nwith confirmed endometriosis through laparoscopy (Mu et al., \n2016; Mu et al., 2017; Marchandot et al., 2022 ). After adjusting for \nother factors, the study found that women with endometriosis had \na relative risk (RR) of 1.14 (95% confidence interval [CI] 1.09–1.18) \nfor developing hypertension. Conversely, women with arterial \nhypertension had an RR of 1.29 (95% CI 1.18– 1.41) for having \nlaparoscopically confirmed endometriosis. This has led to various \nhypotheses, with inflammation being a key component in the \npathogenesis of hypertension, which is also associated with \nendometriosis (Marchandot et al., 2022 ). According to the results \nof the studies, it also became clear that 30% of the reported cases of \nassociation between hypertension and endometriosis were due to \nthe effects of treatment. Namely, an earlier period of surgery and \nhysterectomy /ovariectomy. It has been established that the risk of \nhypertensive disorders in women increases due to a decrease in the \nproduction of sex hormones or after ovariectomy. It is worth noting \nthat the use of nonsteroidal anti -inflammatory drugs (NSAIDs), \nwhich are commonly prescribed to alleviate pelvic pain, has been \nfound to elevate blood pressure and can serve as a significant \nconfounding factor (Blue et al., 2018). In a study conducted by \nOkoth et al., they observed 56,090 women with endometriosis and \ncompared them to a control group of 223,669 individuals. After \nadjusting for other variables, they identified an adjusted odds ratio \n(aOR) of 1.12 (95% CI 1.07 –1.17) for hypertension among women \nwith endometriosis. This suggests that endometriosis \nindependently contributes to an increased risk of gestational \nhypertension and preeclampsia (Okoth et al., 2020). \n \nDyslipidaemia \nObservational studies have provided substantial evidence \nshowcasing a robust association between an elevated atherogenic \nlipid profile and endometriosis. In particular, these data are \ndescribed in detail in the work of Mu et al. The focus of this study \nwas on the health of nurses II (NHSII; n = 116,430). The findings \nrevealed a 25% higher risk of hypercholesterolemia in women with \nendometriosis (95% CI 1.21-1.30), as well as a 22% increased risk of \nlaparoscopically confirmed endometriosis in women with \nhypercholesterolemia (95% CI 1.15- 1.31). Another Nurses' Health \nSurvey conducted in Japan involving 49,927 women (2001- 07) \nconfirmed a 30% increase in the likelihood of hypercholesterolemia \nin women with endometriosis (95% CI 1.15-1.47). It is worth noting \nthat in the course of this work, an adjustment for related factors was \nnot taken into account (Melo et al., 2010; Mu et al., 2017). \nIn a cross-sectional study conducted by Melo et al., the lipid profile \nof 120 women was examined, with 40 of them having confirmed \nendometriosis through laparoscopy. The results indicated elevated \nlevels of total cholesterol, LDL cholesterol, triglycerides, and HDL \ncholesterol (Mu et al., 2017). In the course of additional studies of \nthe lipid profile in endometriosis, contradictory r esults were \nobtained. Tan et al. effectively reviewed the results of nine studies \ninvestigating RRS dyslipidemia in women wit h endometriosis. It is \nimportant to approach their findings with caution due to several \nfactors. Firstly, the study included a relatively small sample size of \npatients. Additionally, there were variations in the parameters \nmeasured and the timing of these measurements, which may impact \nthe interpretation of the results (Tan and Almaria, 2018). \nIn the course of preclinical studies, a change in the lipid profile of \nblood serum in mice with endometriosis was revealed. The \nfollowing reports also confirmed that a key role in the pathogenesis \nof endometriosis is played by impaired metabolism of \nphospholipids and sphingolipids (Chen et al., 2021). Sphingolipids \nplay crucial roles in various cellular processes such as proliferation, \nmaturation, and apoptosis. In a study by Lee et al., they \ndemonstrated significant alterations in the metabolic flow of \nsphingolipids in women with endometriosis. The researchers \nobserved increased regulation of specific sphingolipid enzymes \n(sphingomyelin synthase 1, sphingomyelinase 3, and \nglucosylceramide synthase) in endometriotic residues. This \ncorresponded to elevated levels of glucosylceramide, decreased \nlevels of sphingomyelin, and reduced apoptosis in the \nendometrium. Ceramides, which serve as secondary mediators in \nthe apoptotic cascade and precursors for other sphingolipids, were \nfound to be elevated in the peritoneal fluid of infertile women with \nendometriosis. This causes the formation of reactive oxygen species \nand leads to cytotoxicity (Lee et al., 2014; Sanvicens and Cotter, \n2006). Other studies have also demonstrated the key role of \nsphingolipids in the pathogenesis of stroke, hypertension, \nmyocardial infarction and diabetes. Thanks to the data obtained, it \ncan be assumed that sphingolipids can function as intermediaries of \ninter-organ and intercellular communication. Moving forward, it \nbecomes crucial to investi gate the involvement of sphingolipids in \nendometriosis and determine if sphingolipids affected by \nendometriosis contribute to a systemic pro-inflammatory and pro-\noxidant cascade. This cascade, in turn, may lead to dysfunction in \nvarious organs, including those related to the cardiovascular system \n(Alessenko et al., 2018; Borodzicz et al., 2015). \n \nObesity \nAlthough a correlation has been observed between endometriosis \nand lower body mass index (BMI), a few limited studies have hinted \nat the contrary. The clinical manifestation of a low BMI in women \nwith endometriosis can be attributed to significant factors such as \nthe depletion of fat stem cells, anorexigenic effects resulting from  \n  \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nFigure 1. Potential association between endometriosis and atherosclerosis. \n \n\n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nalterations in liver gene expression, and the initiation of lipid \ndysfunction and fat loss (Zolbin et al., 2019; Goetz et al., 2016). \n \nSmoking, air pollution exposure, and diabetes \nAlthough tobacco smoking is widely recognized as a risk factor for \ncoronary heart disease, there is ongoing debate regarding its \nconnection to endometriosis. Also, some studies have suggested \nthat smoking may reduce the risk of endometriosis, but in \nsubsequent studies, the link between endometriosis and tobacco \nsmoking habits has been refuted. Also, the connection between \nendometriosis and exposu re to pollutants remains presumptive. \nOnly one NHSII study did not show an increased risk of \nendometriosis. as for the effects of air pollution (Helbig et al., 2021). \nAt the moment, there has not been a proven link between diabetes \nand endometriosis, even despite the potential coincidence of \nmolecular pathways between them. Based on the analysis \nconducted in NHSII, there was no identified link between \nlaparoscopically confirmed endometriosis and the development of \ntype 2 diabetes, as determined through multivariate analysis. \nHowever, there is ongoing controversy regarding the potential risk \nof gestational diabetes mellitus in women with endometriosis  \n(Farland et al., 2021). \n \nResults \nTo establish and maintain endometriotic lesions, several \ncardiovascular drugs were tested on animal models. But despite the \nfact that the results were promising in animal models, their use in \nhuman clinical trials was severely limited. \nStatins are recognized for their ability to lower cholesterol levels and \ntheir anti- inflammatory effects. In relation to endometriosis, \nresearch conducted on human endometriosis stromal cell cultures \nhas demonstrated that statins can influence cell signali ng. By \nundergoing statin therapy, apoptosis (cell death) is increased, while \nproliferation is reduced. Moreover, the therapy also hampers cell \nadhesion and mobility, along with diminishing angiogenesis and \nimpeding stromal cell invasion (Taylor et al., 2017). Recent studies \nhave highlighted the significant involvement of platelets in both the \noverall development of endometriosis and specifically in \nfibrogenesis. It was found that antiplatelet therapy prevents the \nprogressive development of endometriosis. epithelial-mesenchymal \ntransition, transdifferentiation of fibroblasts into myofibroblasts \nand metaplasia of smooth muscles (Xiao et al., 2020). Consequently, \na reduction in the size of endometriotic lesions and fibrogenesis has \nbeen observed. Recently, researchers have suggested the use of low-\ndose aspirin in preclinical studies as a potential treatment for \ninfertility associated with endometriosis. This is attributed to its \nability to combat progesterone resistance. \nMoreover, women with endometriosis often experience heightened \npsychological stress, which contributes to tumor growth and \nmetastasis. In a mouse model, the blockade of Beta- adrenergic \nreceptors effectively eliminated the stimulating effect of chronic \nstress, leading to the suppression of ADRB2 and CREB activation \n(Long et al., 2016). As a result, angiogenesis and proliferatio n were \nsuppressed. Another study demonstrated that perioperative \nadministration of propranolol in a mouse model significantly \nimpeded the growth of intentionally neglected residual \nendometriotic lesions following the initial operation. Similarly, the \nuse of telmisartan inhibited vascularization, reduced immune cell \nactivity, and hindered the growth of endometriosis -like lesions in \nmice. \n \nLimitations \nOne limitation pertains to the predominantly observational nature \nof the studies included in the analysis. The reliance on observational \ndata may introduce biases and confounding variables that could \ninfluence the strength and direction of the reported ass ociations. \nAdditionally, the generalizability of findings from observational \nstudies to broader populations or diverse demographic groups may \nbe limited. \nAnother constraint to be mindful of is the potential for publication \nbias within the literature reviewed. Studies with positive findings \nare more likely to be published, leading to an overrepresentation of \nsignificant results in the analysis. This bias cou ld skew the overall \ninterpretation of the relationship between chronic inflammation, \nendometriosis, and atherosclerosis. \nThe review may also be constrained by the availability and quality \nof the studies included. Variability in study methodologies, sample \nsizes, outcome measures, and reporting standards across the \nliterature could impact the robustness and reliability of the  \nconclusions drawn in the review. Moreover, the potential for \nheterogeneity among the included studies may limit the ability to \nperform meta-analyses or draw definitive conclusions. \nFurthermore, the review's scope may be constrained by the existing \nbody of literature on the topic. Limited research focusing \nspecifically on the interconnection between chronic inflammation, \nendometriosis, and atherosclerosis may restrict the depth of \nanalysis and comprehensive understanding of the mechanisms \nunderlying these associations. \nLastly, given the evolving nature of research in this field, the \nreview's findings and conclusions may be subject to change as new \nstudies are published and novel insights emerge. Continued updates \nand revisions to the review may be necessary to incorporat e the \nlatest evidence and address emerging limitations. \nDespite these constraints, the review serves as a valuable synthesis \nof current knowledge on the complex interplay between chronic \ninflammation, endometriosis, and atherosclerosis, highlighting \nareas for further investigation and potential clinical applications. \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nIn addition to the limitations already discussed, it is important to \nacknowledge that the inclusion of studies published only in the last \nfew years may introduce a potential bias towards recent findings, \noverlooking important earlier research. By favoring more recent \nstudies, the review may inadvertently neglect valuable insights and \nfoundational research that could provide critical context and \nhistorical perspective on the link between chronic inflammation, \nendometriosis, and atherosclerosis. \n \nConclusion \nAtherosclerosis is a multifactorial pathology, and endometriosis is \nalso a complex pathology. Inflammation is a cornerstone of both \ndisorders. In this review, we observed the adherent points of \nendometriosis and atherosclerosis, which is not limited to \ninflammation itself, but with numerous associated molecules, \nmechanisms, and even risk factors. Dysregulation of interferon -g \nproduction is the main association between endometriosis and \natherosclerosis, that is confirmed by the range of studies. \nFurthermore, women diagnosed with endometriosis have a higher \nlikelihood of experiencing microvascular dysfunction and \ndeveloping atherosclerosis.  \nThe main limitation of this study is the fact that this review is \nnarrative, not systematic. Our goal was to overview the broad range \nof potential connections at different levels. Also, it is worth \nmentioning, that further studies are needed to understand the \ndetails of vascular aspects of endometriosis, and the inflammatory \nprocesses underlie the linkage of two pathologies.  \nUnderstanding the relationship between endometriosis and an \nincreased risk of microvascular dysfunction and atherosclerosis \nsuggests integrating assessments of arterial stiffness and \ninflammatory markers in the clinical evaluation of women with \nendometriosis. This holistic approach can aid in early detection of \ncardiovascular risk and guide preventive measures. \nThe review indicates that statins, cholesterol-lowering medications, \nand metformin could hold promise in managing endometriosis by \nleveraging their anti -inflammatory properties, hormone \nmodulation effects, and cytokine reduction capabilities. \nInvestigating the efficacy of these medications as therapeutic \ninterventions for endometriosis is a pivotal area for future research. \nDelving into the genetic connections between atherosclerotic \ncardiovascular disease and endometriosis offers insights into shared \ngenes and pathways, potentially leading to tailored treatments for \nindividuals with both conditions. Further exploration of co mmon \ngenetic pathways could pave the way for personalized therapeutic \nstrategies. \nThe role of microRNAs in regulating gene expression and their \nimpact on both endometriosis and atherosclerosis opens new \navenues for diagnostic and therapeutic approaches. Understanding \nhow microRNA dysfunction contributes to the pathophysiology of \nthese conditions may unveil novel targeted treatments. \nRecognizing the impact of endometriosis on ovarian function and \nits association with early menopause has implications for hormone \nreplacement therapy (HRT) decisions in women with \nendometriosis during the menopausal transition. Considering the \ncardiovascular risks linked to early menopause in individuals with \nendometriosis can inform treatment choices. \nExploring the links between endometriosis and cardiovascular risk \nfactors like hypertension, dyslipidemia, obesity, and lifestyle factors \nsuch as smoking, air pollution exposure, and diabetes provides a \ncomprehensive understanding of the interplay of these factors in \nthe overall health of individuals with endometriosis. \nIn conclusion, further research probing the mechanisms \nconnecting chronic inflammation, endometriosis, and \natherosclerosis is vital for advancing our understanding of these \nintricate conditions and devising targeted interventions to enhance \npatient outcomes. An interdisciplinary approach to studying these \nconnections presents opportunities for innovative treatments and \ncomprehensive care strategies. By integrating perspectives and \nexpertise from diverse fields such as cardiology, gynecology, \nimmunology, and  molecular biology, researchers can explore the \ninterconnected pathways and mechanisms underlying both \ndiseases. This collaborative approach allows for a more holistic \nexamination of how chronic inflammation, hormonal factors, \ngenetic predispositions, and lifestyle choices contribute to the \ndevelopment and progression of atherosclerosis and endometriosis. \nBy leveraging the insights and methodologies of different \ndisciplines, researchers can uncover novel connections, identify \ncommon risk factors, and develo p more effective diagnostic tools \nand treatment strategies that address the complex interplay between \nthese conditions. Embracing an interdisciplinary perspective not \nonly enriches the scientific discourse but also paves the way for \ninnovative research ini tiatives and personalized healthcare \napproaches that consider the intricate web of factors influencing the \npathogenesis and management of atherosclerosis and \nendometriosis. \n \nAuthor contribution \nA.V.P. conceptualized, V.N.S., M.A.P., Y.S.C., A.Y.P., A.N.O. \nwrote, drafted, reviewed, edited, prepared the graph of the article. \nAll authors have read and agreed to the published version of the \nmanuscript. \n \nAcknowledgment  \nThis research was funded by Russian Science Foundation (grant \nnumber 20-15-00337). The work was supported by the Ministry of \nScience and Higher Education of the Russian Federation within the \nframework of the state order (Project No. 122030200531-3). \n\nANGIOTHERAPY                                    REVIEW \n \nhttps://doi.org/10.25163/angiotherapy.839556                                                                                                    1–13 | ANGIOTHERAPY | Published online Mar 14, 2024 \n \nCompeting financial interests  \nThe authors have no conflict of interest. \n \nReferences \nAlessenko, A. V., Lebedev, А. Т., & Kurochkin, I. N. (2018). Rol' sfingolipidov v serdechno -\nsosudistykh patologiiakh [The role of sphingolipids in cardiovascular \npathologies]. Biomeditsinskaia khimiia, 64(6), 487 – 495. \nhttps://doi.org/10.18097/PBMC20186406487  \nBjorkman, S., & Taylor, H. S. (2019). MicroRNAs in endometriosis: biological function and \nemerging biomarker candidates†. 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(2019). \nAdipocyte alterations in endometriosis: reduced numbers of stem cells and \nmicroRNA induced alterations in adipocyte metabolic gene expression. \nReproductive biology and endocrinology : RB&E, 17(1), 36. \nhttps://doi.org/10.1186/s12958 -019-0480-0","source_license":"CC0","license_restricted":false}