Targeting TRPV1 and TRPV2 for potential therapeutic interventions in cardiovascular disease

Cardiovascular disease is a leading cause of morbidity and mortality worldwide, encompassing a variety of cardiac and vascular conditions. Transient receptor potential vanilloid (TRPV) channels, specifically TRPV type 1 (TRPV1) and TRPV type 2 (TRPV2), are relatively recently described channels found throughout the body including within and around the cardiovascular system. They are activated by a variety of stimuli including high temperatures, stretch, and pharmacologic and endogenous ligands. The TRPV1 channel has been found to be an important player in the pathway of the detection of chest pain after myocardial injury. Activation of peripheral TRPV I via painful stimuli or capsaicin has been shown to have cardioprotective effects, whereas genetic abrogation of TRPV1 results in increased myocardial damage after ischemia and reperfusion injury in comparison to wild-type mice. Furthermore, blood pressure changes have been noted upon TRPV1 stimulation. Similarly, the TRPV2 channel has also been associated with changes in blood pressure and cardiac function depending on how and where the channel is activated. Interestingly, overexpression of TRPV2 channels in the heart induces dystrophic cardiomyopathy; however, stimulation under physiologic conditions leads to improved cardiac function. Probenecid, a TRPV2 agonist, has been studied as a model therapy for its inotropic effects and potential use in the treatment of cardiomyopathy. In this review, we present an up to date account of the growing evidence that supports the study of TRPV1 and TRPV2 channels as targets for therapeutic agents of cardiovascular diseases.