Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients

• Published in: Atherosclerosis 2015-09, Vol.242 (1), p.167-173
• Main Authors: Victor, Victor M, Rovira-Llopis, Susana, Bañuls, Celia, Diaz-Morales, Noelia, Lopez-Domenech, Sandra, Escribano-López, Irene, Rios-Navarro, Cesar, Alvarez, Angeles, Gomez, Marcelino, Rocha, Milagros, Hernandez-Mijares, Antonio
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biomarkers - blood; Cardiovascular; Cell Adhesion - drug effects; Cell Adhesion Molecules - blood; Cells, Cultured; Coculture Techniques; Cytokines - blood; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - immunology; Endothelial Cells - drug effects; Endothelial Cells - immunology; Endothelial Cells - metabolism; Endothelium; Female; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - immunology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Inflammation Mediators - blood; Leukocyte; Leukocyte Rolling - drug effects; Leukocytes - drug effects; Leukocytes - immunology; Leukocytes - metabolism; Metformin; Metformin - therapeutic use; Mitochondria; PCOS; Polycystic Ovary Syndrome - blood; Polycystic Ovary Syndrome - diagnosis; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - immunology; Spain; Time Factors; Treatment Outcome; Type 2 diabetes; Young Adult
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2015.07.017

Abstract Objective We aim to assess the effect of metformin treatment on metabolic parameters, endothelial function and inflammatory markers in polycystic ovary syndrome (PCOS) subjects. Methods The study population consisted of 40 reproductive-age women with PCOS, who underwent treatment with metformin during a 12-week period, and their corresponding matched controls (n = 44). We evaluated endocrinological parameters, adhesion molecules (vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1) and E-selectin) and proinflammatory cytokines (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα)) in serum. In addition, interactions between human umbilical vein endothelial cells and polymorphonuclear (PMN) cells were assessed by flow chamber microscopy. In addition, a group of type 2 diabetes patients who underwent treatment with metformin during a 12-week period was incorporated into the study. Results Metformin produced beneficial effects on PCOS patients by decreasing polymorphonuclear (PMN) rolling flux and adhesion. It also decreased levels of ICAM-1, E-selectin, IL-6 and ΤΝFα. In addition, metformin induced an improvement of endocrine and anthropometric parameters in PCOS subjects by reducing glucose, follicle-stimulating hormone (FSH) and androstendione, and by increasing dehydroepiandrosterone-sulfate (DHEA-S). Metformin also had beneficial effects in type 2 diabetic subjects by reducing body weight, waist circumference and PMN adhesion, and by increasing PMN rolling velocity. Conclusion Our results highlight the modulating effect of metformin on leukocyte/endothelium interactions. These findings may explain the potential beneficial effect of metformin in reducing the risk of vascular events in PCOS patients and in insulin resistance conditions.