Atorvastatin exerts inhibitory effect on endothelial senescence in hyperlipidemic rats through a mechanism involving down-regulation of miR-21-5p/203a-3p

作者：Zhang, Jie-Jie; Zhang, Yin-Zhuang; Peng, Jing-Jie; Li, Nian-Sheng; Xiong, Xiao-Ming; Ma, Qi-Lin; Luo, Xiu-Ju; Liu, Bin^*; Peng, Jun

来源：Mechanisms of Ageing and Development, 2018, 169: 10-18.

DOI：10.1016/j.mad.2017.12.001

• Atorvastatin
• Hyperlipidemia
• Endothelial senescence
• miR-21-5p
• miR-203a-3p

Statins are reported to exert benefits on endothelial function through a mechanism involving in prevention of endothelial senescence. This study aims to explore whether atorvastatin exerts inhibitory effect on endothelial senescence in hyperlipidemic rats or ox-LDL-treated HUVECs through a mechanism involving suppress of miR-21-5p/203a-3p expression and their downstream pathway. The rats were fed with high-fat diet to establish a hyperlipidemic model, which showed art increase in plasma lipids and endothelial senescence, accompanied by the elevation in plasma levels of miR-21-5p/203a-3p, down-regulation of Drpl and up-regulation of p53 in the aorta of hyperlipidemic rats; these phenomena were reversed by atorvastatin. Next, HUVECs were incubated with ox-LDL to establish a senescent model in vitro. Consistent with the finding in vivo, atorvastatin treatment decreased the level of miR-21-5p and miR-203a-3p in the ox-LDL-treated HUVECs, restored Drpl expression and mitochondrial function, as well as suppressed p53 and p16 expression and endothelial senescence. Based on these observations, we conclude that atorvastatin exerts inhibitory effect on endothelial senescence in hyperlipidemic rats through a mechanism involving down-regulation of miR-21-5p/203a-3p, which leads to the restoration of Drpl level and recovery of mitochondrial function. Our findings highlight a novel non-lipid effect for atorvastatin besides its function in modulation of lipids.

• 出版日期2018-1
• 单位中南大学