{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T20:57:24Z","timestamp":1785272244345,"version":"3.55.0"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Objective: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder with an increased risk for cardiovascular disease (CVD) that is enhanced by obesity. This study sought to determine whether a panel of cardiovascular risk proteins (CVRPs) would be dysregulated in overweight\/obese PCOS patients, highlighting potential biomarkers for CVD in PCOS. Methods: In this exploratory cross-sectional study, plasma levels of 54 CVRPs were analyzed in women with PCOS (n = 147) and controls (n = 97). CVRPs were measured using the SOMAscan proteomic platform (version 3.1), with significant proteins identified through linear models, regression analysis, and receiver operating characteristic (ROC) analysis. Analysis on BMI-matched subsets of the cohort were undertaken. Functional enrichment and protein\u2013protein interaction analyses elucidated the pathways involved. Results: Eleven CVRPs were dysregulated in PCOS (whole set, without matching for body mass index (BMI) or insulin resistance (IR)): leptin, Interleukin-1 receptor antagonist protein (IL-1Ra), polymeric immunoglobulin receptor (PIGR), interleukin-18 receptor (IL-18Ra), C-C motif chemokine 3 (MIP-1a), and angiopoietin-1 (ANGPT1) were upregulated whilst advanced glycosylation end product-specific receptor, soluble (sRAGE), bone morphogenetic protein 6 (BMP6); growth\/differentiation factor 2 (GDF2), superoxide dismutase [Mn] mitochondrial (MnSOD), and SLAM family member 5 (SLAF5) were downregulated versus the controls. In BMI-matched (overweight\/obese, BMI \u2265 26 kg\/m2) subset analysis, six CVRPs were common to the whole set: ANGPT1 and IL-1Ra were upregulated; and sRAGE, BMP6, GDF2, and Mn-SOD were downregulated. In addition, lymphotactin (XCL1) was upregulated and placenta growth factor (PIGF), alpha-L-iduronidase (IDUA), angiopoietin-1 receptor, and soluble (sTie-2) and macrophage metalloelastase (MMP12) were downregulated. A subset analysis of BMI-matched plus insulin resistance (IR)-matched women revealed only upregulation of tissue factor (TF) and renin in PCOS, potentially serving as biomarkers for cardiovascular risk in overweight\/obese women with PCOS. Conclusions: A combination of upregulated obesity-related CVRPs (ANGPT1\/IL\/1Ra\/XCL1) and downregulated cardioprotective proteins (sRAGE\/BMP6\/Mn-SOD\/GDF2) in overweight\/obese PCOS women may contribute to the increased risk for CVD. TF and renin upregulation observed in the BMI- and IR-matched limited sample PCOS subgroup indicates their potential risk of CVD.<\/jats:p>","DOI":"10.3390\/biom15010004","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T09:48:58Z","timestamp":1735033738000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome"],"prefix":"10.3390","volume":"15","author":[{"given":"Manjula","family":"Nandakumar","sequence":"first","affiliation":[{"name":"Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Das","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-2231","authenticated-orcid":false,"given":"Thozhukat","family":"Sathyapalan","sequence":"additional","affiliation":[{"name":"Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3917","authenticated-orcid":false,"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5887-7257","authenticated-orcid":false,"given":"Stephen L.","family":"Atkin","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00404-024-07607-x","article-title":"Global prevalence of polycystic ovary syndrome in women worldwide: A comprehensive systematic review and meta-analysis","volume":"310","author":"Salari","year":"2024","journal-title":"Arch. 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