Abstract
The biological effects of microRNAs (miRNAs) and TNF-α in atherosclerosis have been widely studied. The circulating miR-17-92 cluster has been recently shown to be significantly downregulated in patients with injured vascular endothelium. However, it remains unclear whether the miR-17-92 cluster plays a significant role in vascular endothelial repair. The aim of this study was to investigate the relationship between the miR-17-92 cluster and TNF-α-induced endothelial cell apoptosis. We determined that the down-regulation of miR-19b level among patients with coronary artery disease was consistent with miRNA expression changes in endothelial cells following 24 h of TNF-α treatment. In vitro, the overexpression of miR-19b significantly alleviated the endothelial cells apoptosis, whereas the inhibition of miR-19b significantly enhanced apoptosis. The increased levels of Afap1 and caspase7 observed in our apoptosis model could be reduced by miR-19b, and this effect could be due to miR-19b binding 3'-UTRs of Afap1 and caspase7 mRNA. Therefore our results indicate that miR-19b plays a key role in the attenuation of TNF-α-induced endothelial cell apoptosis and that this function is closely linked to the Apaf1/caspase-dependent pathway.