Attenuated macrophage activation mediated by microRNA-183 knockdown through targeting NR4A2.

Abstract

Atherosclerosis is considered a chronic inflammatory disease, and macrophages function as important mediators in the development of atherogenesis. MicroRNA (miR)-183 is a small non-coding RNA that acts as a novel tumor suppressor and has recently been proposed to affect cardiac hypertrophy. However, the exact role and underlying mechanism of miR-183 in macrophage activation remain unknown. In the present study, miR-183 showed upregulated expression in atheromatous plaques and in bone marrow-derived macrophages (BMDMs) subjected to stimulation with oxidized low-density lipoproteins. Using a miR-183 loss-of-function strategy, it was demonstrated that miR-183 knockdown significantly increased resolving M2 macrophage marker expression but decreased proinflammatory M1 macrophage marker expression, as well as attenuated NF-κB activation. Moreover, decreased foam-cell formation accompanied by upregulation of genes involved in cholesterol efflux and downregulation of genes implicated in cholesterol influx was found in BMDMs transfected with a miR-183 inhibitor. Mechanistically, macrophage activation mediated by miR-183 silencing was partially attributed to direct upregulation of NR4A2 expression in BMDMs. Thus, the present study suggests that neutralizing miR-183 may be a potential therapeutic strategy for the treatment of atherosclerosis.