TRPV4 channels: physiological and pathological role in cardiovascular system

Area of Science:

• Cardiovascular Physiology
• Ion Channel Biology
• Molecular Medicine

Background:

• Transient Receptor Potential Vanilloid 4 (TRPV4) channels are non-selective cation channels permeable to Ca(2+), Na(+), and Mg(2+).
• TRPV4 channels are widely expressed throughout the cardiovascular system, including endothelial cells, cardiac fibroblasts, vascular smooth muscles, and peri-vascular nerves.
• Their broad expression suggests a pivotal role in maintaining cardiovascular homeostasis.

Purpose of the Study:

• To review the evidence and potential mechanisms by which TRPV4 channels influence diverse cardiovascular functions and pathologies.
• To highlight the involvement of TRPV4 in processes such as arteriogenesis, cardiac remodeling, and pulmonary hypertension.

Main Methods:

• This review synthesizes existing research and experimental evidence.
• It discusses the molecular and physiological mechanisms underlying TRPV4 channel function in the cardiovascular system.

Main Results:

• TRPV4 channels critically regulate flow-induced arteriogenesis and TGF-β1-induced differentiation of cardiac fibroblasts.
• They mediate hypoxia-induced proliferation of pulmonary artery smooth muscle cells and progression of pulmonary hypertension.
• TRPV4 channels maintain flow-induced vasodilation and preserve vascular function via KCa channels and release of NO, CGRP, and substance P.

Conclusions:

• TRPV4 channels play a multifaceted role in cardiovascular homeostasis, influencing vascular tone, cardiac remodeling, and disease progression.
• Understanding TRPV4 mechanisms offers potential therapeutic targets for cardiovascular diseases.
• Further research is warranted to fully elucidate the complex roles of TRPV4 in cardiovascular health and disease.