Metformin regulates differentiation of bone marrow-derived endothelial progenitor cells via multiple mechanisms

Abstract

Objective: The aim of this study was to investigate the effect of metformin on endothelial progenitor cells (EPCs) differentiation and the possible mechanisms.

Methods: EPCs were treated with metformin and differentiation, migration and tube formation of EPCs were evaluated. Moreover, we also assessed the AMPK-mTOR-p70S6K pathway, AMPK related autophagy pathway and eNOS-NO pathway to explore the mechanisms.

Results: Metformin treatment could significantly increase differentiation of EPCs. On the mechanisms, increased level of AMPKand eNOS phosphorylation, LC3 expression and NO production, and decreased mTOR, p70 S6K as well as TGF-β expression were found in EPCs. The AMPK inhibitor compound C, Atg5 knocking-down and eNOS inhibitor l-NAME could reverse the effect exerted by metformin.

Conclusions: Our results here showed that metformin could regulate the differentiation of EPCs. Autophagy related pathway and AMPK-eNOS-NO pathway were involved in the mechanisms.

Keywords: Adenosine monophosphate activated protein kinase; Autophagy; Differentiation; Endothelial nitric oxide synthase; Endothelial progenitor cells; Metformin.