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

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

Author information

1
Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; Department of Physiology, University of Valencia, Valencia, Spain; Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Spain. Electronic address: Victor.Victor@uv.es.
2
Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain.
3
Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
4
Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Spain.
5
Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Spain; Fundación General de Universidad de Valencia, Valencia, Spain.
6
Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Spain. Electronic address: Milagros.Rocha@uv.es.
7
Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain. Electronic address: hernandez_antmij@gva.es.

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.

KEYWORDS:

Endothelium; Leukocyte; Metformin; Mitochondria; PCOS; Type 2 diabetes

[Indexed for MEDLINE]

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