Role of TRPV2 in the organization of cardiac plasticity

Abstract

The heart maintains pump function by remodeling in response to changes in mechanical forces caused by heartbeats and hemodynamic loading. For example, the heart shows the compensative hypertrophy when it’s hemodynamic stress increases, such as with hypertension. This is because cardiomyocytes exhibit plasticity via mechanotransduction, and a reduction in this ability leads to heart failure. However, the mechanisms that organization of plasticity during cardiomyocyte growth are not clear. We defined "cardiac resilience" as the state in which hearts maintain plasticity in response to changes in hemodynamic load. Previously, we have shown that transient receptor potential cation channel vanilloid-family type 2 (TRPV2) is a key molecule in cardiomyocyte mechanotransduction and is crucial for the maintenance of cardiac physiology. In this symposium, we will show that TRPV2 is significantly involved in the organization of cardiomyocyte plasticity. Mice deficient in TRPV2 from juvenile age exhibited small cardiac morphology and weak contractility as adults. The cardiomyocytes of these TRPV2-deficient mice had abnormal dyadic structure and reduced Ca²⁺ handling associated with E-C coupling. In addition, TRPV2-deficient mice had an attenuated IGF-1R/Akt/mTOR pathway and did not show hypertrophy in response to IGF-1 administration. These TRPV2cKO hearts did not show an adaptive hypertrophic response to increased hemodynamic stress, resulting in heart failure. These results indicate that TRPV2 is an essential molecule for the maturation of the young heart into a heart with plasticity to hemodynamic stress.