Ankrd1 regulates endogenous cardiac regeneration in mice by modulating cyclin D1.

Restoration of the expression of factors regulating neonatal heart regeneration in the adult heart can promote myocardial repair. Therefore, investigations of the regulatory factors that play key roles in neonatal heart regeneration are urgently needed for the development of cardiac regenerative therapies. In our previous study, we identified ankyrin repeat domain 1 (Ankrd1) through multiomics analysis in a neonatal mouse model of cardiac regeneration and hypothesized that Ankrd1 plays a regulatory role in neonatal heart regeneration. In the present study, we aimed to determine the role of Ankrd1 in neonatal heart regeneration and adult myocardial repair. Our findings confirmed that Ankrd1 could mediate cardiomyocyte proliferation and that Ankrd1 knockdown in cardiomyocytes inhibited myocardial regeneration after apical resection in neonatal mice. Furthermore, we found that cardiomyocyte-specific Ankrd1 overexpression promoted cardiac repair and cardiac function recovery after adult myocardial infarction (MI). Mechanistically, Ankrd1 could regulate the cell cycle of cardiomyocytes and significantly mediate cardiac regeneration, at least in part, through cyclin D1. Overall, our study demonstrates that Ankrd1 is an effective target for achieving cardiac repair after MI, providing new ideas for the treatment of ischemic heart disease in the future.