Role of TRPV2 in mediating and maintaining stress resilience of the heart

The heart has adynamic compensatory mechanism for hemodynamic stress. This adaptive response to stress depends on cardiac resilience. However, the details of the molecular mechanisms underlying cardiac resilience and the mechanisms by which it is acquired remain unclear. In this review, we focus on TRPV2, a candidate molecule for mechanical stress sensors in cardiomyocytes, and its role in cardiac growth and maturation and in the adult heart using drug-induced TRPV2-deficient mice. TRPV2-mediated activation of the transcription factors SRF and MEF2c is an important pathway that regulates structural and functional maturation of cardiomyocytes. TRPV2 is also an essential factor for the maintenance of the intercalated discs, a site of structural and functional contact between neighboring cardiomyocytes. The increased contractile function of individual cardiomyocytes and the maturation of structural and functional contacts between cells are feedback as mechanical stress, suggesting that the heart develops hemodynamic resilience. In addition, hearts deficient in TRPV2 from an early age developed heart failure due to a failure of adaptive response to the hemodynamic load produced by long-term administration of phenylephrine. These findings suggest that TRPV2 mediates stress resilience in mouse cardiomyocytes. In contrast, these TRPV2-deficient hearts did not show structural or functional changes in response to pressure-overload induced by transverse aortic constriction. These suggest that TRPV2 acts as a mechanotransduction key molecule in the adult mouse heart in response to hemodynamic loading. Advances in this area are expected to provide more options for strategies to treat heart failure conditions.