Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome
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 pat...
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2024-12-01
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| author | Manjula Nandakumar Priya Das Thozhukat Sathyapalan Alexandra E. Butler Stephen L. Atkin |
| author_facet | Manjula Nandakumar Priya Das Thozhukat Sathyapalan Alexandra E. Butler Stephen L. Atkin |
| author_sort | Manjula Nandakumar |
| collection | DOAJ |
| description | 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–protein 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 ≥ 26 kg/m<sup>2</sup>) 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. |
| format | Article |
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| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-8c8a7c75450a4de2bcb5343b3517212a2025-01-24T13:24:49ZengMDPI AGBiomolecules2218-273X2024-12-01151410.3390/biom15010004Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary SyndromeManjula Nandakumar0Priya Das1Thozhukat Sathyapalan2Alexandra E. Butler3Stephen L. Atkin4Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, BahrainResearch Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, BahrainAcademic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RU, UKResearch Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, BahrainResearch Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, BahrainObjective: 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–protein 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 ≥ 26 kg/m<sup>2</sup>) 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.https://www.mdpi.com/2218-273X/15/1/4polycystic ovary syndromePCOScardiovascular riskbiomarkersproteomics |
| spellingShingle | Manjula Nandakumar Priya Das Thozhukat Sathyapalan Alexandra E. Butler Stephen L. Atkin Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome Biomolecules polycystic ovary syndrome PCOS cardiovascular risk biomarkers proteomics |
| title | Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome |
| title_full | Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome |
| title_fullStr | Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome |
| title_full_unstemmed | Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome |
| title_short | Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome |
| title_sort | cardiovascular risk biomarkers in women with and without polycystic ovary syndrome |
| topic | polycystic ovary syndrome PCOS cardiovascular risk biomarkers proteomics |
| url | https://www.mdpi.com/2218-273X/15/1/4 |
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