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Atherosclerosis. 2019 Jan;280:28-36. doi: 10.1016/j.atherosclerosis.2018.11.024. Epub 2018 Nov 10.

MicroRNA-142-3p improves vascular relaxation in uremia.

Author information

1
Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
2
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria; Department of Phoniatrics, ENT University Hospital Graz, Medical University of Graz, Austria.
3
Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
4
Department of Dialysis, Clinic for Internal Medicine, University Clinical Centre Maribor, Slovenia; Faculty of Medicine, University of Maribor, Maribor, Slovenia.
5
Department of Radiology, University Clinical Centre Maribor, Slovenia.
6
Faculty of Medicine, University of Maribor, Maribor, Slovenia; Department of Nephrology, Clinic for Internal Medicine, University Clinical Center Maribor, Slovenia.
7
Institute of Chemistry Analytical Chemistry, Karl-Franzens University Graz, Graz, Austria.
8
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.
9
Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Graz, Austria.
10
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Austria.
11
Department of Internal Medicine, Intensive Care Unit, Medical University of Graz, Austria. Electronic address: philipp.eller@medunigraz.at.

Abstract

BACKGROUND AND AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Arterial stiffness; Endothelium dysfunction; Pulse wave velocity; Vascular calcification

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