ALDH2 delays ventricular pressure overload-induced heart failure by promoting cardiomyocyte proliferation in mice

The adult mammalian heart is a terminally differentiated organ in which the majority of cardiomyocytes are in a state of cell cycle arrest, rendering them incapable of effectively proliferating to replace damaged cells. ALDH2, an enzyme known for alleviating oxidative stress, has been demonstrated to play a critical role in cardiac protection. However, whether ALDH2 regulates cardiomyocyte proliferation has not been conclusively established. We found that activation of ALDH2 activity significantly promotes cardiomyocyte proliferation and extends the proliferation window during early postnatal development in neonatal mice. Furthermore, administration of Alda-1 to activate ALDH2 in adult mice subjected to transverse aortic constriction markedly enhanced cardiomyocyte proliferation and delayed the onset of pressure overload-induced heart failure. In summary, our findings identify ALDH2 as a potential target for regulating cardiomyocyte proliferation and offer a novel therapeutic approach for treating heart failure.