标题: MicroRNA-92a Mediates Endothelial Dysfunction in CKD
作者: Shang, Fenqing
Wang, Shen-Chih
Hsu, Chien-Yi
Miao, Yifei
Martin, Marcy
Yin, Yanjun
Wu, Chih-Cheng
Wang, Yun-Ting
Wu, Gaihong
Chien, Shu
Huang, Hsien-Da
Tarng, Der-Cherng
Shiu, Yan-Ting
Cheung, Alfred K.
Huang, Po-Hsun
Chen, Zhen
Shyy, John Y. -J.
生物资讯及系统生物研究所
Institude of Bioinformatics and Systems Biology
公开日期: 1-十一月-2017
摘要: 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.
URI: http://dx.doi.org/10.1681/ASN.2016111215
http://hdl.handle.net/11536/144030
ISSN: 1046-6673
DOI: 10.1681/ASN.2016111215
期刊: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume: 28
起始页: 3250
结束页: 3260
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