MicroRNA-92a Mediates Endothelial Dysfunction in CKD
MicroRNA-92a Mediates Endothelial Dysfunction in CKD
复制标题
MicroRNA-92a 介导 CKD 中的内皮功能障碍
DOI：
10.1681/asn.2016111215
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发表时间：
2017-11-01
影响因子：
13.6
通讯作者：
Shyy, John Y. -J.
中科院分区：
文献类型：
--
作者：
Shang, Fenqing;Wang, Shen-Chih;Shyy, John Y. -J.
CKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules. The antioxidant N-acetylcysteine inhibited these vasculopathic properties. In rats, adenine-induced CKD associated with increased levels of miR-92a in aortas, serum, and CD144(+) endothelial microparticles. Furthermore, CD144(+) microparticles from human uremic serum contained more miR-92a than those from control serum. Additional analysis showed a positive correlation between serum levels of miR-92a and indoxyl sulfate in a cohort of patients with ESRD undergoing hemodialysis. Collectively, our findings suggest that the uremic toxins accumulated in CKD can upregulate miR-92a in ECs, which impairs EC function and predisposes patients to CVD.
