Macrophage autophagy regulated by miR-384-5p-mediated control of Beclin-1 plays a role in the development of atherosclerosis

摘要

Macrophages play an essential and complicated role in the pathogenesis of atherosclerosis. However, the regulation of macrophage autophagy as well as it role in the development of atherosclerosis is unclear. MicroRNA-384-5p (miR-384-5p) is a new miRNA that attracted attention very recently, while its effects on Beclin-1 and cell autophagy has not been reported. Here, we studied macrophage autophagy in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of Beclin-1 and the levels of miR-384-5p in the purified F4/80+ macrophages from mouse aorta. Prediction of the binding between miR-384-5p and 3’-UTR of Beclin-1 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. We found that HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as NOR mice) did not. Compared to NOR mice, HFD mice had significantly lower levels of macrophage autophagy, and significantly higher levels of macrophage death, resulting from decreases in Beclin-1. The decreases in Beclin-1 in macrophages were due to HFD-induced increases in miR-384-5p, which suppressed the translation of Bectlin-1 mRNA via 3’-UTR binding. Together, our study suggests that upregulation of miR-384-5p by HFD may impair the Beclin-1-mediated protection of macrophages through autophagy to accelerate the development of atherosclerosis.