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

Atherosclerosis. 2015 Sep;242(1):167-73. doi: 10.1016/j.atherosclerosis.2015.07.017. Epub 2015 Jul 10.


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.

Keywords: Endothelium; Leukocyte; Metformin; Mitochondria; PCOS; Type 2 diabetes.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • 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
  • 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 Rolling / drug effects*
  • Leukocytes / drug effects*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Metformin / therapeutic use*
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / diagnosis
  • Polycystic Ovary Syndrome / drug therapy*
  • Polycystic Ovary Syndrome / immunology
  • Spain
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Biomarkers
  • Cell Adhesion Molecules
  • Cytokines
  • Inflammation Mediators
  • Metformin