LncRNA H19/miR-let-7 axis participates in the regulation of ox-LDL-induced endothelial cell injury via targeting periostin.

Oxidized-low density lipoprotein (ox-LDL)-induced endothelial cell dysfunction is a crucial event in the pathogenesis of atherosclerosis (AS). Long noncoding RNAs (lncRNAs) have been shown to play important roles in this process. The purpose of this study was to investigate the biological effects of lncRNA H19 on the ox-LDL-induced endothelial cell injury and to explore the underlying molecular mechanisms. In the present study, the expression of H19 in the serum of patients with AS and in the ox-LDL-treated human umbilical vein endothelial cells (HUVECs) was significantly up-regulated. H19 knockdown by transfection with H19 siRNAs in ox-LDL-treated HUVECs remarkably promoted cell viability, suppressed the secretion of interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α, decreased the expression of vascular cell adhesion molecule 1 (VCAM1), intercellular adhesion molecule 1 (ICAM1) and E-selectin, reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) levels, and reduced cell apoptosis. Moreover, H19 knockdown significantly down-regulated the ox-LDL-induced expression of periostin, but did not affect the expression of let-7a, which directly targets the 3'-UTR of periostin mRNA. In addition, periostin overexpression partly reversed the biological effects of H19 knockdown in ox-LDL-treated HUVECs, which were almost recapitulated by let-7 overexpression. In conclusion, these data suggest that H19 knockdown suppressed ox-LDL-induced inflammation, apoptosis and oxidative stress in HUVECs, which may be related to the down-regulation of periostin by interfering with let-7 bioavailability.