Long intergenic noncoding RNA p21 mediates oxidized LDL‑induced apoptosis and expression of LOX‑1 in human coronary artery endothelial cells

Zhou,Tao; Chen,Xiaofang

doi:10.3892/mmr.2017.7623

Long intergenic noncoding RNA p21 mediates oxidized LDL‑induced apoptosis and expression of LOX‑1 in human coronary artery endothelial cells

Authors:
- Tao Zhou
- Xiaofang Chen
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Affiliations: Department of Cardiology, The Third Affiliated Hospital, South Medical University, Guangzhou, Guangdong 510630, P.R. China, Nursing Department, The Third Affiliated Hospital, South Medical University, Guangzhou, Guangdong 510630, P.R. China
Published online on: September 26, 2017 https://doi.org/10.3892/mmr.2017.7623
Pages: 8513-8519

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Abstract

Atherosclerosis is the most common pathological cause of cardiovascular diseases, and endothelial dysfunction has a vital role. It has been suggested that inhibiting endothelial cell apoptosis induced by oxidized low‑density lipoprotein (ox‑LDL), an essential atherosclerotic factor, is a potential novel therapeutic strategy against atherosclerosis. Previous studies have revealed that endothelial lectin‑like ox‑LDL receptor‑1 (LOX‑1) and long intergenic noncoding RNA p21 (lincRNA‑p21) may serve as therapeutic targets for atherosclerosis and associated cardiovascular disorders. The present study investigated the role of lincRNA‑p21 in oxLDL‑induced apoptosis and expression of LOX‑1 in human coronary artery endothelial cells (HCAECs). Primary HCAECs were treated with ox‑LDL (30, 60 or 90 µg/ml) for 24 or 48 h, and the expression of lincRNA‑p21, LOX‑1 and cell apoptosis rate were measured. Ox‑LDL dose‑ and time‑dependently induced the expression of lincRNA‑p21 and LOX‑1 and apoptosis in HCAECs. Lentiviral overexpression of lincRNA‑p21 markedly increased oxLDL‑induced apoptosis and the expression of LOX‑1 in HCAECs. Additionally, the effect was largely blocked by selective protein kinase C (PKC) inhibitor, rottlerin. However, lentiviral knockdown of lincRNA‑p21 markedly decreased oxLDL‑induced apoptosis and the expression of LOX‑1. In addition, overexpression and knockdown of lincRNA‑p21 markedly increased and decreased oxLDL‑induced PKCδ activity/phosphorylation, respectively. In conclusion, to the best of our knowledge, the present study provides the first evidence indicating that lincRNA‑p21 is a major mediator of oxLDL‑induced apoptosis and expression of LOX‑1 in human vascular endothelial cells, and acts via activation of PKCδ. These results provide insights into the role of lincRNA‑p21 in the pathogenesis of atherosclerosis.

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