TRP channels in cardiac mechano-redox coupling and diseases

Abstract

Reactive oxygen species (ROS) produced by mechanically stretching cardiomyocytes is a crucial mediator to increase contractile force in accordance with the Frank-Starling law. However, excessive ROS production leads to oxidative stress, contributing to myocardial atrophic remodeling and cellular damage. NADPH oxidase, the primary enzyme responsible for ROS production localized on the plasma membrane and organelle membranes, plays a key role in membrane-oriented ROS signaling. Two isoforms of NADPH oxidase, Nox2 (constitutive) and Nox4 (inducible), are predominantly expressed in cardiomyocytes, each playing unique roles in different contexts. Recent studies have revealed that Nox proteins form protein signaling complexes with transient receptor potential (TRP) channel proteins, amplifying ROS signaling in hearts. This review presents the putative mechanism of protein-protein interaction between TRP and Nox and their pathophysiological significance in hearts and discusses therapeutic strategies targeting TRP-Nox protein interactions for the treatment of heart failure.