MicroRNA‑1929‑3p participates in murine cytomegalovirus‑induced hypertensive vascular remodeling through Ednra/NLRP3 inflammasome activation

Abstract

MicroRNAs (miRNAs) play an important role in the development of vascular remodeling in essential hypertension (EH) by mediating the effects of human cytomegalovirus (HCMV) on the vascular system. Therefore, the aim of the present study was to investigate the effects of murine cytomegalovirus (MCMV) infection on blood pressure and vascular function in mice, in order to elucidate the role of miR-1929-3p in this process. For model development, 7-month-old C57BL/6J mice were infected with the Smith strain of MCMV, and MCMV DNA, IgG and IgM were detected. Subsequently, blood pressure was measured via the carotid artery, and the morphological changes of the aorta were evaluated by hematoxylin and eosin and Masson's trichrome staining. miR-1929-3p transfection was performed using an adeno-associated virus packaged vector and the changes in vascular structure were then observed. The levels of nitric oxide (NO) and endothelial NO synthase were also assessed with colorimetry. Vascular remodeling and expression of NLRP3 inflammasome pathway-related proteins were detected by immunohistochemistry and western blotting. Endothelin-1 (ET-1), interleukin (IL)-1β and IL-18 were assayed by ELISA. The results revealed that MCMV infection increased the blood pressure, promoted vascular remodeling, caused endothelial cell injury, and downregulated miR-1929-3p. However, these effects were alleviated by miR-1929-3p overexpression, which downregulated endothelin A receptor (Ednra) and NLRP3 inflammasome, as well as endothelial injury- and vascular remodeling-related genes. Taken together, the findings of the present study indicated that overexpression of miR-1929-3p may improve MCMV-induced vascular remodeling, possibly via the deactivation of the NLRP3 inflammasome by ET-1/Ednra.

Microrna-342-3p Loaded by Human Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Attenuates Deep Vein Thrombosis by Downregulating EDNRA

“…More intriguingly, the increase trend of EDNRA expression has been tested in vascular smooth muscle cells suffered from lipopolysaccharide [37]. Wei Zhou et al have validated that elevation of miR-1929-3p decreases blood pressure and attenuates endothelial cell injury in part by decreasing EDNRA expression in hypertensive vascular remodeling [14]. It has been implicated that increased EDNRA function is deleterious for cystic brosis airway [38].…”

MicroRNA-342-3p lOaded by Human Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Attenuates Deep Vein Thrombosis by Downregulating EDNRA Running Title: Exosome Delivery of miR-342-3p in DVT

“…More intriguingly, the increase trend of EDNRA expression has been tested in vascular smooth muscle cells suffered from lipopolysaccharide [37]. Wei Zhou et al have validated that elevation of miR-1929-3p decreases blood pressure and attenuates endothelial cell injury in part by decreasing EDNRA expression in hypertensive vascular remodeling [14]. It has been implicated that increased EDNRA function is deleterious for cystic brosis airway [38].…”

Interleukin-1β in Multifactorial Hypertension: Inflammation, Vascular Smooth Muscle Cell and Extracellular Matrix Remodeling, and Non-Coding RNA Regulation

“…In this study, they found that mice overexpressing miRNA-1929-3p exhibited less vascular remodeling and NLRP3 inflammasome activation. This likely occurred by miRNA-1929-3p mediated suppression of the endothelin A receptor (ETRA) which has been shown to be critical in endothelin-mediated blood pressure changes and inflammasome activation [18,68]. Similarly, it was found that miR155-5p limits oxidative stress and IL-1β in the SHR rat model [69].…”

“…For instance, recent reports suggest that IL-1β not only participates in the pro-inflammatory response in the vessels, it also influences vascular smooth muscle cell (VSMC) phenotype and functions and vascular remodeling in multiple types of hypertension through inflammatory-dependent or independent mechanisms [16]. In addition, another new avenue of research in this area is related to the regulation of IL-1β by non-coding RNAs (ncRNAs) in hypertension [17,18]. These new findings also suggest that analogous regulatory mechanisms may be involved in the pathogenesis of various hypertensive disorders.…”