Deletion of the microRNA-degrading nuclease, translin/trax, prevents pathogenic vascular stiffness.

Deletion of the microRNA-degrading nuclease, translin/trax, prevents pathogenic vascular stiffness.
Am J Physiol Heart Circ Physiol. 2019 Oct 18;:
Authors: Tuday E, Nomura Y, Ruhela D, Nakano M, Fu X, Shah A, Roman B, Yamaguchi A, An SS, Steenbergen C, Baraban JM, Berkowitz DE, Das S
Abstract
Vascular stiffness plays a key role in the pathogenesis of hypertension. Recent studies indicatethat the age associated reduction in miR-181b levels in vascular smooth muscle cells (VSMCs)contributes to increased vascular stiffness. As these findings suggest that inhibiting degradation of miR-181b might prevent vascular stiffening, we have assessed whether themicroRNA-degrading translin/trax (TN/TX) complex mediates degradation of miR-181b in the aorta.We found that TN-/- mice display elevated levels of miR-181b expression in the aorta. Therefore, we tested if TN deletion prevents vascular stiffening in a mouse model of hypertension, induced by chronic high salt intake (4% NaCl in drinking water for 3 weeks; HSW). TN-/- mice subjected to HSW stress do not show increased vascular stiffness, as monitored by pulse wave velocity and tensile testing. The protective effect of TN deletion in the HSW paradigm appears to be mediated by its ability to increase miR-181b in the aorta since HSW decreases levels of miR-181b in WT mice, but not in TN KO mice.We demonstrate for the first time that interfering with microRNA degradation can have abeneficial impac...

Source: American Journal of Physiology. Heart and Circulatory Physiology - October 17, 2019 Category: Physiology Authors: Tuday E, Nomura Y, Ruhela D, Nakano M, Fu X, Shah A, Roman B, Yamaguchi A, An SS, Steenbergen C, Baraban JM, Berkowitz DE, Das S Tags: Am J Physiol Heart Circ Physiol Source Type: research