MicroRNA-92a Mediates Endothelial Dysfunction in CKD

• Published in: Journal of the American Society of Nephrology Vol. 28; no. 11; pp. 3251 - 3261
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.11.2017
• Subjects: Animals; Basic Research; Endothelial Cells - physiology; Female; Humans; Male; MicroRNAs - blood; MicroRNAs - physiology; Middle Aged; Rats; Rats, Wistar; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - physiopathology; chronic kidney disease; endothelial cells; microRNA-92; oxidative stress
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2016111215

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 -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.