TRPV4 channels: physiological and pathological role in cardiovascular system

Abstract

TRPV4 channels are non-selective cation channels permeable to Ca(2+), Na(+), and Mg(2+) ions. Recently, TRPV4 channels have received considerable attention as these channels are widely expressed in the cardiovascular system including endothelial cells, cardiac fibroblasts, vascular smooth muscles, and peri-vascular nerves. Therefore, these channels possibly play a pivotal role in the maintenance of cardiovascular homeostasis. TRPV4 channels critically regulate flow-induced arteriogenesis, TGF-β1-induced differentiation of cardiac fibroblasts into myofibroblasts, and heart failure-induced pulmonary edema. These channels also mediate hypoxia-induced increase in proliferation and migration of pulmonary artery smooth muscle cells and progression of pulmonary hypertension. These channels also maintain flow-induced vasodilation and preserve vascular function by directly activating Ca(2+)-dependent KCa channels. Furthermore, these may also induce vasodilation and maintain blood pressure indirectly by evoking the release of NO, CGRP, and substance P. The present review discusses the evidences and the potential mechanisms implicated in diverse responses including arteriogenesis, cardiac remodeling, congestive heart failure-induced pulmonary edema, pulmonary hypertension, flow-induced dilation, regulation of blood pressure, and hypoxic preconditioning.

Dual contribution of TRPV4 antagonism in the regulatory effect of vasoinhibins on blood-retinal barrier permeability: diabetic milieu makes a difference

“…Ca 2+ entry through TRPV4 has been also shown to increase lung endothelial cell permeability by disrupting cell-cell or cell-matrix adhesion 34,35 . A mechanism through which TRPV4 activation evokes the reorganization of actin cytoskeleton that associates with increased permeability may involve NO release 36,37 . Inversely, blockage of TRPV4 channels inhibits eNOS activation by phosphorylation 38 and mitigates pulmonary edema 39 .…”

“…We therefore tested this possibility and further postulated that vasoinhibins may regulate BRB permeability by blocking TRPV4. This novel concept is rooted in the fact that vasoinhibins exert effects opposite to the ones induced by TRPV4 activation to regulate capillary endothelial barrier (i.e., intracellular Ca 2+ rise, eNOS phosphorylation, NO release, cytoskeleton reorganization 36,43–46 ).…”

Activation of transient receptor potential vanilloid 4 involves in hypoxia/reoxygenation injury in cardiomyocytes

“…3 Therefore, TRPV4 may have an important role in modulating the function of the cardiovascular system in physiological and pathological conditions. 4 …”

Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction

“…Furthermore, other ion channels cannot be discounted as additional channels, that are described in endothelial and smooth muscle cells (e.g. TRPV4, voltage-gated Ca 2+ channels, ORAIs, TRPM6/M7, TRPC6) [5, 44], could also mediate this effect. Endothelial Derived Hyperpolarizing Factors (EDHFs) contribute to regulation of vascular tone [37, 62].…”