The endothelium contributes to the maintenance of vasodilator
tone by releasing endothelium-derived relaxing factors, including
nitric oxide (NO). In hypertension, endothelial nitric oxide
synthase (eNOS) produces less NO and could be one of the
contributing factors to the increased peripheral vascular
resistance. Agonist-induced Ca2+ entry is essential for the
activation of eNOS. The transient receptor potential vanilloid
type 4 (TRPV4) channel, a Ca2+-permeant cation channel, is
expressed in the endothelial cells and involved in the regulation
of vascular tone. The present study aimed to investigate the role
of TRPV4 channel in endothelium-dependent NO-mediated
relaxation of the resistance artery in hypertensive rats. Using
a wire myograph, relaxation response to the TRPV4 activator,
4α-phorbol-12,13-didecanoate (4αPDD) was assessed in
mesenteric arteries obtained from Wistar-Kyoto (WKY) and
spontaneously hypertensive rats (SHRs). Compared to WKY, SHR
demonstrated a significantly attenuated 4αPDD-induced
endothelium-dependent NO-mediated relaxation. Immunohistochemical analysis revealed positive staining for TRPV4 in the
endothelium of mesenteric artery sections in both WKY and SHR.
Furthermore, TRPV4 mRNA and protein expressions in SHR were
significantly lower than their expression levels in WKY rats.
We conclude that 4αPDD-induced endothelium-dependent
NO-mediated vasorelaxation is reduced in SHR and downergulation of TRPV4 could be one of the contributing mechanisms.
Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles due to multiple etiologies. Emilin 1 plays a determinant role in fibers formation, but its role in the progression of GMC remains unclear. The present study was aimed to search for the predictive role and regulatory mechanism of Emilin 1 on GMC. Here, Protein and mRNA expression of Emilin 1 were decreased in GMC tissues compared to normal muscle tissues. Using the analysis of target prediction, Emilin 1 was observed to be a potential downstream sponge of miR-491-5p. In comparison to Emilin 1, miR-491-5p showed an aberrant elevation in GMC tissues, which was further proven to have a negative correlation with Emilin 1. The direct binding of miR-491-5p to Emilin 1 mRNA was confirmed by luciferase reporter gene assay, and miR-491-5p mimics inhibited, while miR-491-5p inhibitor promoted the protein expression and secretion of Emilin 1 in contraction bands (CB) fibroblasts. Additionally, miR-491-5p mimics promoted the expression of cyclin-dependent kinase 2 and cyclin D1 and the proliferation of CB fibroblasts, which could be reversed by Emilin 1 overexpression. Mechanistically, miR-491-5p mimics possibly activated transforming growth factor β1 (TGF-β1)/Smad3 signal cascade via binding to 3’-untranslated region of Emilin 1 mRNA, thereby promoting the progression of fibrosis of CB fibroblasts. Collectively, miR-491-5p inhibited Emilin 1 expression, and subsequently promoted CB fibroblasts proliferation and fibrosis via activating TGF-β1/Smad3 signal axis. MiR-491-5p might be a potentially effective biomarker for predicting GMC, providing a novel therapeutic strategy for GMC.