Role of Known Transient Receptor Potential Vanilloid Channels in Modulating Cardiac Mechanobiology.

Michael Miller,Timothy Domeier,Jack Rubinstein,Sheryl E Koch,Adam Veteto

doi:10.3389/fphys.2021.734113

Abstract

The transient receptor potential (TRP) channels have been described in almost every mammalian cell type. Several members of the Vanilloid (TRPV) subtype have been found to play important roles in modulating cardiac structure and function through Ca2+ handling in response to systemic and local mechanobiological cues. In this review, we will consider the most studied TRPV channels in the cardiovascular field; transient receptor potential vanilloid 1 as a modulator of cardiac hypertrophy; transient receptor potential vanilloid 2 as a structural and functional protein; transient receptor potential vanilloid 3 in the development of hypertrophy and myocardial fibrosis; and transient receptor potential vanilloid 4 in its roles modulating the fibrotic and functional responses of the heart to pressure overload. Lastly, we will also review the potential overlapping roles of these channels with other TRP proteins as well as the advances in translational and clinical arenas associated with TRPV channels.

Highlights

Since their initial discovery in the late 1990s, the transient receptor potential (TRP) family of channels has been described in almost every mammalian cell type (Nilius and Szallasi, 2014)
The first study to demonstrate a critical role for TRPV4 in mediating myocardial ischemia/reperfusion (I/R) injury was performed in mice with left anterior descending (LAD) coronary artery ligation, in the presence and absence of TRPV4-specific inhibitor HC067047 (Dong et al, 2017)
Action potential duration (APD) increased following pericardiotomy was shortened using TRPV4 antagonism. These results suggest TRPV4 plays an arrhythmogenic role in atrial fibrillation (AF) via induction of adverse atrial remodeling and/or changes in atrial cardiomyocyte Ca2+ flux

Summary

INTRODUCTION

Since their initial discovery in the late 1990s, the transient receptor potential (TRP) family of channels has been described in almost every mammalian cell type (Nilius and Szallasi, 2014). Using a TAC animal model, Morine et al (2016) and Koch et al (2017) separately demonstrated a similar increase and translocation of the TRPV2 channel in murine cardiomyocytes derived from the left ventricle These effects were not found to occur in response to angiotensin or beta-adrenergic stimulation (Koch et al, 2017), strongly supporting its role in modulating hypertrophic signaling through mechanosensitive, as opposed through intracellular signaling, pathways. The first study to demonstrate a critical role for TRPV4 in mediating myocardial ischemia/reperfusion (I/R) injury was performed in mice with left anterior descending (LAD) coronary artery ligation, in the presence and absence of TRPV4-specific inhibitor HC067047 (Dong et al, 2017) Both TRPV4 mRNA and protein expression were shown to be elevated in a time-dependent manner following I/R injury, and TRPV4 antagonism decreased infarct size and increased ejection fraction 24 h following I/R. Adapala et al demonstrated the functional role of TRPV4 in mediating adverse cardiac remodeling following myocardial infarction at the in vivo, tissue, and cell level

CONCLUSION AND TRANSLATIONAL OUTLOOK

AUTHOR CONTRIBUTIONS