Upregulation of miR-142-5p in atherosclerotic plaques and regulation of oxidized low-density lipoprotein-induced apoptosis in macrophages.

Abstract

MicroRNA (miR)-142-5p is a member of the miR-142 family, which have been shown to be associated with tumors, stem cells and disorders of the immune system. However, the role of miR-142-5p in atherosclerosis has yet to be investigated. In the present study, an atherosclerotic apolipoprotein E-deficient (apoE−/−) mouse model was constructed and fed a high-fat diet. The expression levels of miR-142-5p in the murine atherosclerotic plaques were detected by gene microarray analysis. In addition, an in vitro assay was used to determine the expression levels of miR-142-5p in human endothelial cells, smooth muscle cells and macrophages, which were treated with oxidized low-density lipoprotein (ox-LDL). Furthermore, a miR-142-5p inhibitor and mimic was transfected into cultured human macrophages, in order to observe the effects on transforming growth factor-β2 (TGF-β2) expression. The effects of co-transfection of the miR-142-5p inhibitor or mimic with TGF-β2, in human macrophages, on the rate of apoptosis was analyzed. The expression levels of miR-142-5p were 6.84-fold higher in mice with stable atherosclerotic plaques, and 2.69-fold higher in mice with vulnerable atherosclerotic plaques, as compared with the controls. Furthermore, the expression levels of miR-142-5p were upregulated in the cultured human macrophages. The percentage of apoptotic cells was lowest in the macrophages transfected with both TGF-β2 and miR-142-5p inhibitors and treated with ox-LDL. The expression levels of miR-142-5p were upregulated in the atherosclerotic plaques of the apoE−/− mice. The findings of the present study have shown that the upregulation of miR-142-5p expression may regulate apoptosis in human macrophages by targeting TGF-β2. This effect may have an important role in the progression of atherosclerosis.