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 |
显示于类别: | Articles |