Key result
miR-142-3p restores vascular relaxation in uremic mice and links to reduced arterial stiffness in humans.
Why the study?
Does synthetic miR-142-3p mimic improve vascular relaxation in uremic models?
Does synthetic miR-142-3p mimic improve vascular relaxation in uremic models?
miR-142-3p represents a potential pharmacological target to prevent endothelial dysfunction and arterial stiffness in end-stage renal disease.
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.
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Kétszeri et al. (2018) studied End-stage renal disease (ESRD). Synthetic miR-142-3p mimic was evaluated on Acetylcholine-mediated vascular relaxation and carotid-femoral pulse-wave velocity. Intravenous injection of synthetic miR-142-3p mimic restored acetylcholine-mediated vascular relaxation in uremic mice, and blood miR-142-3p was negatively associated with arterial stiffness in humans.
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