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

Li,Yangwei; Zhang,Kang; Mao,Wei

doi:10.3892/mmr.2018.8411

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

Authors:
- Yangwei Li
- Kang Zhang
- Wei Mao
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Affiliations: Department of Cardiovascular Medicine, The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, Department of Cardiovascular Medicine, Dongyang People's Hospital, Jinhua, Zhejiang 322103, P.R. China
Published online on: January 9, 2018 https://doi.org/10.3892/mmr.2018.8411
Pages: 4645-4650

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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.

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