Inhibition of miR-34a prevents endothelial cell apoptosis by directly targeting HDAC1 in the setting of atherosclerosis

Abstract

Despite recent medical advances, atherosclerosis is a global burden accounting for numerous mortalities and hospital admissions. MicroRNAs (miRNAs/miRs) regulate cardiovascular biology and disease, but the role of microRNA-34a in atherosclerosis remains unclear. In the present study, it was demonstrated that miR-34a was highly expressed in atherosclerotic lesions and oxidized low-density lipoprotein (Ox-LDL)-treated human aortic endothelial cells (HAECs) (atherosclerotic cell model) using reverse transcription-quantitative polymerase chain reaction. The expression of histone deacetylase (HDAC) 1 was reduced in atherosclerotic lesions and Ox-LDL treated HAECs. TargetScan predicted that HDAC1 is the potential target of miR-34a and the double-luciferase reporter assay confirmed that HDAC1 was directly targeted by miR-34a. Furthermore, miR-34a inhibitor significantly enhanced the cell viability of HAECs and the cell apoptosis was suppressed. In addition, the expression of apoptotic-related proteins was detected by western blotting. The results showed that miR-34a inhibitor significantly upregulated B-cell lymphoma 2, procaspase-3, procaspase-9 and proto-oncogene c-Myc protein expression, and downregulated the expression of p21. In contrast, co-transfection of HDAC1-small interfering RNA and miR-34a inhibitor eliminated the effects of miR-34a on HAECs. This indicated that miR-34a inhibitor promoted cell viability and prevented cell apoptosis of HAECs through regulating HDAC1. In conclusion, it was demonstrated that miR-34a promoted atherosclerotic formation by modulating the proliferation and apoptosis of HAECs, and regulating the expression of apoptosis-related proteins by targeting HDAC1.