MicroRNA-92a mediates endothelial dysfunction in CKD

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.