Role of TRPV4 channel in vasodilation and neovascularization

Abstract

The transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca²⁺ -permeable nonselective cation channel, is widely distributed in the circulatory system, particularly in vascular endothelial cells (ECs) and smooth muscle cells (SMCs). The TRPV4 channel is activated by various endogenous and exogenous stimuli, including shear stress, low intravascular pressure, and arachidonic acid. TRPV4 has a role in mediating vascular tone and arterial blood pressure. The activation of the TRPV4 channel induces Ca²⁺ influx, thereby resulting in endothelium-dependent hyperpolarization and SMC relaxation through SK_Ca and IK_Ca activation on ECs or through BK_Ca activation on SMCs. Ca²⁺ binds to calmodulin, which leads to the production of nitric oxide, causing vasodilation. Furthermore, the TRPV4 channel plays an important role in angiogenesis and arteriogenesis and is critical for tumor angiogenesis and growth, since it promotes or inhibits the development of various types of cancer. The TRPV4 channel is involved in the active growth of collateral arteries induced by flow shear stress, which makes it a promising therapeutic target in the occlusion or stenosis of the main arteries. In this review, we explore the role and the potential mechanism of action of the TRPV4 channel in the regulation of vascular tone and in the induction of neovascularization to provide a reference for future research.

Keywords: TRPV4; angiogenesis; arteriogenesis; vasodilation.