Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kétszeri, M; Kirsch, A; Frauscher, B; Moschovaki-Filippidou, F; Mooslechner, AA; Kirsch, AH; Schabhuettl, C; Aringer, I; Artinger, K; Pregartner, G; Ekart, R; Breznik, S; Hojs, R; Goessler, W; Schilcher, I; Müller, H; Obermayer-Pietsch, B; Frank, S; Rosenkranz, AR; Eller, P; Eller, K.
MicroRNA-142-3p improves vascular relaxation in uremia.
Atherosclerosis. 2019; 280(1):28-36
Doi: 10.1016/j.atherosclerosis.2018.11.024
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- Führende Autor*innen der Med Uni Graz
- Eller Philipp
- Co-Autor*innen der Med Uni Graz
- Aringer Ida
- Artinger Katharina
- Eller Kathrin
- Frank Sasa
- Frauscher Bianca
- Kirsch Alexander
- Kirsch Andrijana
- Mooslechner Agnes Anna
- Müller Helmut
- Obermayer-Pietsch Barbara
- Pregartner Gudrun
- Rosenkranz Alexander
- Schilcher Irene Rosa Maria
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- Abstract:
- Chronic 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. We 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. The 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. Taken 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. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
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