Abstract
Transient receptor potential vanilloid 4 (TRPV4) channels are widely expressed in systemic tissues and can be activated by many stimuli. TRPV4, a Ca2+-permeable cation channel, plays an important role in the vasculature and is implicated in the regulation of cardiovascular homeostasis processes such as blood pressure, vascular remodeling, and pulmonary hypertension and edema. Within the vasculature, TRPV4 channels are expressed in smooth muscle cells, endothelial cells, and perivascular nerves. The activation of endothelial TRPV4 contributes to vasodilation involving nitric oxide, prostacyclin, and endothelial-derived hyperpolarizing factor pathways. TRPV4 activation also can directly cause vascular smooth muscle cell hyperpolarization and vasodilation. In addition, TRPV4 activation can evoke constriction in some specific vascular beds or under some pathological conditions. TRPV4 participates in the control of vascular permeability and vascular damage, particularly in the lung capillary endothelial barrier and lung injury. It also participates in vascular remodeling regulation mainly by controlling vasculogenesis and arteriogenesis. This review examines the role of TRPV4 in vascular function, particularly in vascular dilation and constriction, vascular permeability, vascular remodeling, and vascular damage, along with possible mechanisms, and discusses the possibility of targeting TRPV4 for therapy.
Highlights
Increasing evidence has shown that ion channels play numerous important roles in cell homeostasis, allowing the passage of specific ions (Hubner and Jentsch, 2002; Jentsch et al, 2004)
The dysfunction of Transient receptor potential (TRP) channels is associated with endothelial dysfunction, which is reflected by nitric oxide (NO) bioavailability decrease, vascular smooth muscle tonicity dysregulation, endothelial barrier dysfunction, oxidative damage increase, and angiogenic disorder
The current review summarizes reports about the role of Transient receptor potential vanilloid 4 (TRPV4) in vascular dilation and constriction, vascular permeability, vascular remodeling, and vascular damage, and discusses possible mechanisms
Summary
Increasing evidence has shown that ion channels play numerous important roles in cell homeostasis, allowing the passage of specific ions (Hubner and Jentsch, 2002; Jentsch et al, 2004). 4α-PDD decreases the infarct volume, improves the recovery of neurological function, and enhances vasculogenesis and neurogenesis in ischemic stroke rats (Chen et al, 2018) These results suggest that both VSMCs and endothelial cells play important roles in TRPV4-regulated vascular remodeling. Recent evidence suggests that activating pulmonary capillary endothelial TRPV4 channels enhance pulmonary venous pressure-induced edema and TRPV4 blockade prevents the increased vascular permeability and pulmonary edema (Thorneloe et al, 2012), highlighting a pharmacological therapeutic potential of TRPV4 inhibition for pulmonary edema induced by heart failure. TRPV4 channels participate in the KCa3.1-regulated proliferation of human bronchial smooth muscle cells in the process of chronic asthma (Yu et al, 2017), indicating that it is a potential therapeutic target for chronic asthma treatment. Because discrepant effect of TRPV4 on many tissues and systemic TRPV4 blockage may be detrimental, targeting the signaling pathways upstream of TRPV4 activation might be an alternative strategy
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