MicroRNA-92a mediates endothelial dysfunction in CKD

Fenqing Shang, Shen Chih Wang, Chien Yi Hsu, Yifei Miao, Marcy Martin, Yanjun Yin, Chih Cheng Wu, Yun Ting Wang, Gaihong Wu, Shu Chien, Hsien Da Huang, Der Cherng Tarng, Yan Ting Shiu, Alfred K. Cheung, Po Hsun Huang, Zhen Chen, John Y.J. Shyy

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Abstract

CKDis an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress andendothelial dysfunction. MicroRNA-92a (miR-92a) is inducedby 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-CKDserum, induced the levels ofmiR-92a and suppressedthe expression ofmiR-92a targets, includingkey endothelial-protectivemolecules.The antioxidantN-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 serumlevels ofmiR-92a and indoxyl sulfate in a cohort of patientswith 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.

Original languageEnglish
Pages (from-to)3251-3261
Number of pages11
JournalJournal of the American Society of Nephrology
Volume28
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

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ASJC Scopus subject areas

  • Nephrology

Cite this

Shang, F., Wang, S. C., Hsu, C. Y., Miao, Y., Martin, M., Yin, Y., Wu, C. C., Wang, Y. T., Wu, G., Chien, S., Huang, H. D., Tarng, D. C., Shiu, Y. T., Cheung, A. K., Huang, P. H., Chen, Z., & Shyy, J. Y. J. (2017). MicroRNA-92a mediates endothelial dysfunction in CKD. Journal of the American Society of Nephrology, 28(11), 3251-3261. https://doi.org/10.1681/ASN.2016111215