MicroRNA-505 identified from patients with essential hypertension impairs endothelial cell migration and tube formation

Objectives: MicroRNAs are potent regulators of gene expression and may serve as disease markers. This study aimed to identify the plasma microRNA signature in hypertensive patients, which may help better understand the mechanisms underlying the pathogenesis of hypertension and target organ impairment. Methods and results: Plasma samples from three independent cohorts were analyzed to identify circulating microRNA candidates associated with hypertension in patients. The results revealed that the plasma level of hsa-miR-505, a previously reported tumor suppressive microRNA, was significantly elevated in hypertensive patients. Further studies were carried out in endothelial cells to elucidate the functional significance of the enhanced level of hsa-miR-505. The results showed that hsa-miR-505 expression markedly impaired the migration and tube formation of all three types of endothelial cells examined. Moreover, gene expression analyses and luciferase reporter assay revealed that FGF18, a proangiogenic factor, is a target directly regulated by hsa-miR-505 in endothelial cells, which may in part underlie the function of hsa-miR-505 in angiogenic processes. Conclusions: Our findings indicate that hsa-miR-505 is a novel circulating signature of hypertension, which may play a role in angiogenesis. Our results provide mechanistic insights into hypertension-associated pathogenesis and point hsa-miR-505 as a potential target for intervention of hypertension. (C) 2014 Elsevier Ireland Ltd. All rights reserved.