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

摘要

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 mu g/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 PKC delta 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 PKC delta. These results provide insights into the role of lincRNA-p21 in the pathogenesis of atherosclerosis.