Role of the microRNA, miR-206, and its target PIK3C2α in endothelial progenitor cell function - potential link with coronary artery disease

Coronary artery disease is a major cause of morbidity and mortality worldwide. Impaired endothelial function and integrity are major contributory factors to coronary artery disease. MicroRNAs have been proposed to play an important role in coronary artery disease pathogenesis. In the present study, the expression of miR-206 was found to be significantly upregulated in peripheral blood endothelial progenitor cells from patients with coronary artery disease compared to healthy donors. MiR-206 was found to regulate endothelial progenitor cell activities by targeting the protein kinase PIK3C2 alpha, which showed decreased expression in coronary artery disease endothelial progenitor cells. Knockdown of miR-206 in coronary artery disease endothelial progenitor cells rescued their angiogenic and vasculogenic abilities both in vitro and in vivo in a mouse ischemic hindlimb model. Furthermore, knockdown of miR-206 activated not only PIK3C2 alpha, but also the angiogenic signal modulators Akt and endothelial nitric oxide synthase. It is therefore proposed that repression of the phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase signal transduction pathway by miR-206 downregulates angiogenesis contributing to the pathophysiology of coronary artery disease.