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MicroRNA-142-3p improves vascular relaxation in uremia

2018; Elsevier BV; Volume: 280; Linguagem: Inglês

10.1016/j.atherosclerosis.2018.11.024

1879-1484

Máté Kétszeri, Andrijana Kirsch, Bianca Frauscher, Foteini Moschovaki-Filippidou, Agnes A. Mooslechner, Alexander H. Kirsch, Corinna Schabhuettl, Ida Aringer, Katharina Artinger, Gudrun Pregartner, Robert Ekart, Silva Breznik, Radovan Hojs, Walter Goessler, Irene Schilcher, H. Müller, Barbara Obermayer‐Pietsch, Saša Frank, Alexander R. Rosenkranz, Philipp Eller, Kathrin Eller,

Parathyroid Disorders and Treatments

Background and aimsChronic kidney disease (CKD) is strongly associated with a high burden of cardiovascular morbidity and mortality. Therefore, we aimed to characterize the putative role of microRNAs (miR)s in uremic vascular remodelling and endothelial dysfunction.MethodsWe investigated the expression pattern of miRs in two independent end-stage renal disease (ESRD) cohorts and in the animal model of uremic DBA/2 mice via quantitative RT-PCR. Moreover, DBA/2 mice were treated with intravenous injections of synthetic miR-142-3p mimic and were analysed for functional and morphological vascular changes by mass spectrometry and wire myography.ResultsThe expression pattern of miRs was regulated in ESRD patients and was reversible after kidney transplantation. Out of tested miRs, only blood miR-142-3p was negatively associated with carotid-femoral pulse-wave velocity in CKD 5D patients. We validated these findings in a murine uremic model and found similar suppression of miR-142-3p as well as decreased acetylcholine-mediated vascular relaxation of the aorta. Therefore, we designed experiments to restore bioavailability of aortic miR-142-3p in vivo via intravenous injection of synthetic miR-142-3p mimic. This intervention restored acetylcholine-mediated vascular relaxation.ConclusionsTaken together, we provide compelling evidence, both in humans and in mice, that miR-142-3p constitutes a potential pharmacological agent to prevent endothelial dysfunction and increased arterial stiffness in ESRD.