期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 28, 期 11, 页码 3250-3260出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2016111215
关键词
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资金
- US National Institutes of Health [5T32HL007444, R01HL106579]
- Taiwan Ministry of Science and Technology Academic Excellence Program Ministry of Science and Technology [103-2628-B-009-001-MY3, 103-2314-B-195-014, 106-2633-B-009-001, 105-2633-B-009-003]
- City of Hope Beckman Research Institute Start-Up Fund
- National Natural Science Foundation of China [81670452, 81270349]
- [R01DK100505]
- [R01DK088777]
- [K99/R00HL122368]
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.
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