Overexpression of Foxk1 or Foxk2 promoted cardiomyocyte proliferation, significantly improved cardiac function, and reduced fibrotic scar size in adult mice following myocardial infarction.
Does Foxk1 or Foxk2 overexpression improve cardiomyocyte proliferation and heart regeneration in mice after myocardial infarction?
Foxk1 and Foxk2 promote heart regeneration and improve cardiac function after myocardial infarction in mice by enhancing cardiomyocyte proliferation through cell cycle activation and metabolic reprogramming.
Promoting endogenous cardiomyocyte proliferation is a promising strategy for cardiac repair. Identifying key factors that regulate cardiomyocyte proliferation can advance the development of novel therapies for heart regeneration. Here, we identify Foxk1 and Foxk2 as key regulators of cardiomyocyte proliferation, whose expression declines during postnatal heart development. Cardiomyocyte-specific knockout of Foxk1 or Foxk2 impairs neonatal heart regeneration after myocardial infarction (MI) injury. AAV9-mediated Foxk1 or Foxk2 overexpression extends the postnatal cardiomyocyte proliferative window and enhances cardiac repair in adult mice after MI. Mechanistically, Foxk1 and Foxk2 drive cardiomyocyte cell cycle progression by directly activating CCNB1 and CDK1 expression, forming the CCNB1/CDK1 complex that facilitates G2/M transition. Moreover, Foxk1 and Foxk2 promote cardiomyocyte proliferation by upregulating HIF1α expression, which enhances glycolysis and the pentose phosphate pathway (PPP), which further favors cardiomyocyte proliferation. These findings establish Foxk1 and Foxk2 as promising therapeutic targets for cardiac injury. Stimulating endogenous cardiomyocyte proliferation offers a promising approach for treating cardiac injuries. Here, the authors demonstrate that Foxk1 and Foxk2 promote heart regeneration by enhancing cardiomyocyte proliferation through cell cycle activation and metabolic reprogramming, presenting potential therapeutic targets for ischemic heart disease
Cai et al. (Mon,) conducted a other in Myocardial infarction. Foxk1 or Foxk2 overexpression vs. AAV9-GFP was evaluated on Cardiac function and cardiomyocyte proliferation. Overexpression of Foxk1 or Foxk2 promoted cardiomyocyte proliferation, significantly improved cardiac function, and reduced fibrotic scar size in adult mice following myocardial infarction.