Downregulation of microRNA‑34a inhibits oxidized low‑density lipoprotein‑induced apoptosis and oxidative stress in human umbilical vein endothelial cells

Zhong,Xiaoming; Li,Peng; Li,Juan; He,Ruili; Cheng,Guanchang; Li,Yanming

doi:10.3892/ijmm.2018.3663

Downregulation of microRNA‑34a inhibits oxidized low‑density lipoprotein‑induced apoptosis and oxidative stress in human umbilical vein endothelial cells

Authors:
- Xiaoming Zhong
- Peng Li
- Juan Li
- Ruili He
- Guanchang Cheng
- Yanming Li
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Affiliations: Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
Published online on: May 9, 2018 https://doi.org/10.3892/ijmm.2018.3663
Pages: 1134-1144

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Abstract

Oxidized low‑density lipoprotein (ox‑LDL) promotes endothelial cell dysfunction, which is a primary risk factor for the development of atherosclerosis. A previous study reported that microRNA (miRNA/miR)‑34a is upregulated in atherosclerotic samples. However, its function and underlying mechanisms remain to be fully elucidated. In the present study, miRNA microarray analysis was performed to investigate the miRNA expression profile in atherosclerotic plaque tissues and examine the role of miR‑34a in ox‑LDL‑induced apoptosis of human umbilical vein endothelial cells (HUVECs). Cell viability, apoptosis and protein expression was determined by a cell counting kit‑8 assay, flow cytometry and western blot analysis, respectively. It was observed that miR‑34a was upregulated in atherosclerotic plaque tissues and that ox‑LDL treatment significantly increased the levels of miR‑34a in a dose‑dependent manner in the HUVECs. The knockdown of miR‑34a increased the protein expression of B‑cell lymphoma 2 (Bcl‑2) and cell viability, improved mitochondrial membrane potential, and decreased the activity of caspase‑3, number of apoptotic cells and release of cytochrome c from mitochondria in the ox‑LDL‑treated HUVECs. The results also demonstrated that the knockdown of miR‑34a suppressed the levels of ox‑LDL‑induced reactive oxygen species (ROS) in HUVECs. Additionally, it was found that Bcl‑2 was a target of miR‑34a in HUVECs, and that silencing Bcl‑2 abrogated the protective effects of the downregulation of miR‑34a on ox‑LDL‑induced apoptosis. These data indicated that the knockdown of miR‑34a protected against ox‑LDL apoptosis and ROS in HUVECs via inhibiting the mitochondrial apoptotic pathway, suggesting it may offer potential as a biomarker in the clinical diagnosis and as a target for the treatment of atherosclerosis.

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