Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells from patients with coronary artery disease

Endothelial progenitor cells (EPCs) play an important role in vascular repair and maintenance of vascular homeostasis through re-endothelialization and neovascularization. Cardiovascular risk factors that contribute to coronary artery disease (CAD) have been shown to negatively impact EPCs, although the mechanisms are poorly understood. MicroRNAs (miRNAs) which negatively regulate gene expression at the post-transcriptional level have been shown to impact endothelial cell (EC) angiogenic actions, but little is known about their role in modulating EPC function. In this study we first investigated if EPCs expressed EC specific, angiogenesis-related miRNAs; then determined whether the expression of these miRNAs was altered in EPCs from CAD patients as compared with healthy controls. Furthermore, we examined if atorvastatin, known to increase circulating EPC numbers, had any effect on EPC miRNA expression. We found EPCs produced miR-126, miR-130a, miR-221, miR-222 and miR-92a which have thus far been identified as the most important angiogenic miRNAs. Dysregulation of these miRNAs was detected in EPCs from CAD patients and atorvastatin treatment selectively impacted miRNA expression in EPCs.Our data provide evidence that angiogenic miRNAs might play an important role in the control of EPC function, and that their dysregulation might contribute to EPC dysfunction in patients suffering from coronary artery disease. These findings might lead to the development of novel therapeutic modalities for the prevention and treatment of CAD.

Research highlights
► Human endothelial progenitor cells (EPCs) expressed a group of endothelial cell selective angiogenesis-related miRNAs.
► The pro-angiogenic miRNA, miR-126 was down-regulated while the anti-angiogenic miRNAs, miR-221, miR-222 and miR-92a were up-regulated in EPCs from patients with coronary artery disease (CAD) compared with healthy controls.
► The in vitro administration of the HMG-CoA reductase inhibitor atorvastatin enhanced miR-221, miR-222 and miR-92a expression in EPCs from CAD patients while the levels of miR-126 and miR-130a were not affected.