Effects of miR­590 on oxLDL­induced endothelial cell apoptosis: Roles of p53 and NF­κB.

ABSTRACT

Oxidized low­density lipoprotein (oxLDL)­induced endothelial cell apoptosis is considered to be important in atherogenesis. MicroRNA (miR)­590 has been reported to inhibit oxLDL­induced endothelial cell apoptosis. However, the mechanism underlying the inhibition of oxLDL­induced endothelial cell apoptosis by miR­590 remains to be elucidated. In the present study, the expression levels of miR­590 were quantified using reverse transcription­quantitative polymerase chain reaction analysis. Cell apoptosis was investigated using Hoechst staining and flow cytometry, and cell viability was measured using an MTS method. The protein expression levels of p53, B cell lymphoma 2 (Bcl­2), Bcl­2­associated X protein (Bax), caspase­3, lectin­like low­density lipoprotein receptor 1 (LOX­1), p38 mitogen­activated protein kinase (MAPK) and nuclear factor (NF)­κB were quantified using western blot analyses. The results of the present study showed that oxLDL treatment inhibited the expression levels of miR­590 in a time­dependent and concentration­dependent manner. The overexpression of miR­590 inhibited oxLDL­induced endothelial cell apoptosis, expression of p53 and Bax, reduction of Bcl­2 and activation of caspase­3. miR­590 also inhibited the oxLDL­induced upregulation of the expression of LOX­1, overproduction of reactive oxygen species (ROS), phosphoryation of p38MAPK and translocation of NF­κB. These findings demonstrated the anti­apoptotic effects of miR­590 in oxLDL­treated endothelial cells, with the mechanisms underlying the effects of miR­590 involved, in part, in the LOX­1­ROS­p38MAPK­NF­κB signaling cascade and the p53­Bcl­2/Bax­caspase­3 signaling pathway. The present study may provide novel insights into the protective properties of miR­590 in preventing atherosclerosis.