Circulation, Ahead of Print. BACKGROUND:Cardiomyocytes, as highly specialized and differentiated somatic cells, possess a limited capacity for renewal.
Neonatal rodents possess the ability to regenerate cardiomyocytes after injury; however, this regenerative capacity declines rapidly with cardiomyocyte maturation, suggesting an inhibitory network between cellular maturation and cardiomyocyte proliferation. Maturing cardiomyocytes undergo a metabolic shift from predominantly glycolysis in the neonatal state to increased fatty acid oxidation in the mature state, which poses a barrier to cardiomyocyte proliferation and cardiac regenerative repair.
YAP, a transcriptional cofactor regulated by the Hippo signaling pathway, promotes cardiac regenerative repair. We investigated the role of YAP in mediating metabolic remodeling to overcome the cardiomyocyte proliferation barrier and enable cardiac regenerative repair after heart injury.METHODS:We explored how YAP induces metabolic remodeling through single-nucleus RNA sequencing and metabolomic analyses in mice.
Using lipidomic analysis, we demonstrated how YAP remodels the balance of fatty acid catabolism and anabolism. We further used a maternal fat overloading model to stimulate fatty acid oxidation, which activates a maturation program in neonatal cardiomyocytes and counteracts YAP-mediated metabolic dematuration.
Circulation published a clinical update in Cardiology on 09 Mar 2026.
The item focuses on YAP Induces a Prorenewal Metabolic State in Cardiomyocytes.
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