MiR-221-3p inhibits oxidized low-density lipoprotein induced oxidative stress and apoptosis via targeting a disintegrin and metalloprotease-22.

Abstract

Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and apoptosis are considered as a critical contributor to atherosclerosis. MicroRNAs (miRNAs) have been reported versatile functions in all biological processes via directly suppressing target messenger RNA at a posttranscriptional level. Although miRNA-221 has been implied to be involved in the regulation of atherosclerosis, the underlying mechanism remains unclear. Here, we showed that ox-LDL treatment remarkably suppressed the expression of miR-221-3p in a concentration-dependent and time-dependent manner. Transfection of miR-221-3p mimic significantly reduced the foam cell formation and expression of lipid biomarkers, while transfection of the miR-221-3p inhibitor showed completely opposite effects. Moreover, miR-221-3p was also found to inhibit the process of cell apoptosis in macrophages. A disintegrin and metalloprotease-22 (ADAM22) is predicted as a direct target of miR-221-3p, and silencing AMAM22 resulted in a reduced foam cell formation and cell apoptosis. Furthermore, silencing AMAM22 restored the stimulatory effect of the miR-221-3p inhibitor in ox-LDL-induced foam cell formation and apoptosis. These findings suggest that miR-221-3p inhibits ox-LDL and apoptosis via directly targeting ADAM22.