Journal
MOLECULAR MEDICINE REPORTS
Volume 13, Issue 1, Pages 867-873Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2015.4606
Keywords
microRNA-590; endothelial cell; oxidized low-density lipoprotein; atherosclerosis; p53
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Funding
- Construct Program of the Key Discipline in Hunan Province, National Sciences Foundation of China [81300231]
- Hunan Provincial Natural Sciences Foundation of China [13JJ4112]
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Oxidized low-density lipoprotein (oxLDL)-induced endothelial cell apoptosis is considered to be important in atherogenesis. MicroRNA (miR)-590 has been reported to inhibit oxLDL-induced endothelial cell apoptosis. However, the mechanism underlying the inhibition of oxLDL-induced endothelial cell apoptosis by miR-590 remains to be elucidated. In the present study, the expression levels of miR-590 were quantified using reverse transcription-quantitative 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 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3,lectin-like low-density lipoprotein receptor 1 (LOX-1), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B were quantified using western blot analyses. The results of the present study showed that oxLDL treatment inhibited the expression levels of miR-590 in a time-dependent and concentration-dependent manner. The overexpression of miR-590 inhibited oxLDL-induced endothelial cell apoptosis, expression of p53 and Bax, reduction of Bcl-2 and activation of caspase-3. miR-590 also inhibited the oxLDL-induced upregulation of the expression of LOX-1, overproduction of reactive oxygen species (ROS), phosphoryation of p38MAPK and translocation of NF-kappa B. These findings demonstrated the anti-apoptotic effects of miR-590 in oxLDL-treated endothelial cells, with the mechanisms underlying the effects of miR-590 involved, in part, in the LOX-1-ROS-p38MAPK-NF-kappa B signaling cascade and the p53-Bcl-2/Bax-caspase-3 signaling pathway. The present study may provide novel insights into the protective properties of miR-590 in preventing atherosclerosis.
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