MicroRNA-34a regulation of endothelial senescence

MicroRNA-34a regulation of endothelial senescence
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DOI:
10.1016/j.bbrc.2010.07.012
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发表时间:
2010-08-06
影响因子:
3.1
通讯作者:
Yamakuchi, Munekazu
Yamakuchi, Munekazu
中科院分区:
生物学4区
文献类型:
--
作者:
Ito, Takashi;Yagi, Shusuke;Yamakuchi, Munekazu

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Endothelial senescence is thought to play a role in cardiovascular diseases such as atherosclerosis. We hypothesized that endothelial microRNAs (miRNAs) regulate endothelial survival and senescence. We found that miR-34a is highly expressed in primary endothelial cells. We observed that miR-34a expression increases in senescent human umbilical cord vein endothelial cells (HUVEC) and in heart and spleen of older mice. MiR-34a over-expression induces endothelial cell senescence and also suppresses cell proliferation by inhibiting cell cycle progression. Searching for how miR-34a affects senescence, we discovered that SIRT1 is a target of miR-34a. Over-expressing miR-34a inhibits SIRT1 protein expression, and knocking down miR-34a enhances SIRT1 expression. MiR-34a triggers endothelial senescence in part through SIRT1, since forced expression of SIRT1 blocks the ability of miR-34a to induce senescence. Our data suggest that miR-34a contributes to endothelial senescence through suppression of SIRT1. Published by Elsevier Inc.