The role of miRNA-339-5p in the function of vascular endothelial progenitor cells in patients with PCOS. Reproductive biomedicine online RESEARCH QUESTION:miRNA-339 participates in diseases with endothelial progenitor cell (EPC) dysfunction. What is the role of miRNA-339-5p in EPC of polycystic ovary syndrome (PCOS)? DESIGN:Clinical data were collected from 76 controls and 84 PCOS patients. Noradrenaline, asymmetric dimethylarginine (ADMA), advanced glycation end products (AGE) and silent information regulator 1 (SIRT1) in the serum were measured. The functions of EPC and the expressions of PI3K, AKT, SIRT1 and PGC-1α in EPC before and after transfection with miRNA-339-5p mimic or miRNA-339-5p inhibitor were compared. RESULTS:Serum concentrations of noradrenaline, ADMA and AGE were significantly higher (P = 0.009, P = 0.044, P < 0.001) and the SIRT1 concentration was significantly lower (P < 0.001) in PCOS patients, especially obese ones (P = 0.034, P = 0.032, P < 0.001, P = 0.023) than in the control group. When compared with the controls, proliferation of the EPC was slightly lower (without a significant difference), the migration and tubular formation were significantly decreased (P = 0.037, P = 0.011), the expression of miRNA-339-5p in EPC was significantly higher (P = 0.035) and the expressions of PI3K, AKT, SIRT1 and PGC-1α were significantly lower in the PCOS group (mRNA: P = 0.033, P = 0.027, P = 0.027, P = 0.032; protein: P = 0.036, P = 0.028, P = 0.039, P = 0.023). After transfection, the functions of EPC from PCOS patients were best in the miRNA-339-5p inhibitor group, and weakest in the miRNA-339-5p mimic group. The miRNA-339-5p inhibitor group had higher protein expressions of PI3K, AKT and SIRT1 but lower expression of PGC-1α in PCOS patients (P < 0.001, P = 0.030, P = 0.047, P = 0.003). Similar results were obtained from the controls after transfection. CONCLUSION:Increased sympathetic excitation and damage to EPC were observed in PCOS patients, especially obese ones. Up-regulated miRNA-339-5p could inhibit the function of EPC by inhibiting the PI3K/AKT and SIRT1/PGC-1α signalling pathways. 10.1016/j.rbmo.2021.09.017

Oxidative stress and cardiovascular complications in polycystic ovarian syndrome. Hyderali Barkath Nisha,Mala Kanchana European journal of obstetrics, gynecology, and reproductive biology Polycystic ovarian syndrome (PCOS) is a complex endocrine condition which is associated with metabolic and cardiovascular complications. It is elevated to a metabolic disorder with significant long term health ramification due to the high prevalence of insulin resistance (IR), impaired glucose tolerance, type 2 diabetes (T2D), dyslipidemia and numerous cardiovascular risk factors in PCOS women. This article concentrates on the recent developments in the regulation of oxidative stress (OS) in PCOS and on the association between PCOS and CVD outcomes. The prognostic events that define the severity of PCOS and involvement of cardiovascular risk in PCOS include endothelial dysfunction (ED) and impaired cardiac structure. Fact is that, in PCOS women, the circulating biomarkers of OS are in abnormal levels that are independent of overweight, which depicts the participation of OS in the pathophysiology of this common derangement. In addition, hyperglycemia (HG) per se, promotes reactive oxygen species (ROS) generation in PCOS. When the destructive ROS outbalances the concentration of physiological antioxidants, OS occurs. The resultant OS, directly stimulates hyperandrogenism and causes extensive cellular injury, DNA damage and/or cell apoptosis. To further the burden, the total serum antioxidant level in PCOS women is compromised, which diminishes the body's defense against an oxidative milieu. Thus, it is evident that OS regulates several cellular mechanisms in PCOS. Improving our understanding about the regulation of OS, critical role of ROS and protein biomarkers in PCOS should lead to novel therapeutic strategies in addressing PCOS-induced CVD. Besides, it is possible that the beneficial effects of dietary or therapeutic antioxidants have significant clinical relevance in PCOS. 10.1016/j.ejogrb.2015.05.005

Polycystic Ovary Syndrome Fuels Cardiovascular Inflammation and Aggravates Ischemic Cardiac Injury. Circulation BACKGROUND:Reducing cardiovascular disease burden among women remains challenging. Epidemiologic studies have indicated that polycystic ovary syndrome (PCOS), the most common endocrine disease in women of reproductive age, is associated with an increased prevalence and extent of coronary artery disease. However, the mechanism through which PCOS affects cardiac health in women remains unclear. METHODS:Prenatal anti-Müllerian hormone treatment or peripubertal letrozole infusion was used to establish mouse models of PCOS. RNA sequencing was performed to determine global transcriptomic changes in the hearts of PCOS mice. Flow cytometry and immunofluorescence staining were performed to detect myocardial macrophage accumulation in multiple PCOS models. Parabiosis models, cell-tracking experiments, and in vivo gene silencing approaches were used to explore the mechanisms underlying increased macrophage infiltration in PCOS mouse hearts. Permanent coronary ligation was performed to establish myocardial infarction (MI). Histologic analysis and small-animal imaging modalities (eg, magnetic resonance imaging and echocardiography) were performed to evaluate the effects of PCOS on injury after MI. Women with PCOS and control participants (n=200) were recruited to confirm findings observed in animal models. RESULTS:Transcriptomic profiling and immunostaining revealed that hearts from PCOS mice were characterized by increased macrophage accumulation. Parabiosis studies revealed that monocyte-derived macrophages were significantly increased in the hearts of PCOS mice because of enhanced circulating Ly6C monocyte supply. Compared with control mice, PCOS mice showed a significant increase in splenic Ly6C monocyte output, associated with elevated hematopoietic progenitors in the spleen and sympathetic tone. Plasma norepinephrine (a sympathetic neurotransmitter) levels and spleen size were consistently increased in women with PCOS when compared with those in control participants, and norepinephrine levels were significantly correlated with circulating CD14CD16 monocyte counts. Compared with animals without PCOS, PCOS animals showed significantly exacerbated atherosclerotic plaque development and post-MI cardiac remodeling. Conditional silencing in PCOS mice significantly suppressed cardiac inflammation and improved cardiac injury after MI. CONCLUSIONS:Our data documented previously unrecognized mechanisms through which PCOS could affect cardiovascular health in women. PCOS may promote myocardial macrophage accumulation and post-MI cardiac remodeling because of augmented splenic myelopoiesis. 10.1161/CIRCULATIONAHA.123.065827