ArticleCirculation2026
YAP Induces a Prorenewal Metabolic State in Cardiomyocytes.
Article in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Cross-cutting circuits in heart failure with preserved ejection fraction: Integrating adipokine biology, mechanotransduction, and precision targeting.International journal of biological sciences · 2026Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundCardiomyocytes, 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.
methodsWe 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. Using chromatin accessibility (assay for transposase-accessible chromatin with high-throughput sequencing), DNA footprinting, and transcriptional profiling (RNA sequencing), we discovered the key transcription factors that YAP interrupts to reprogram the cardiomyocyte metabolic state.
resultsOur results demonstrate that YAP directs metabolic remodeling of mature cardiomyocytes toward a neonatal-like metabolic state and illustrate the role of fatty acid metabolism in proliferating cardiomyocytes. We found that YAP reduces cardiomyocyte fatty acid utilization, driving fatty acid anabolism and phospholipid biosynthesis. Genome-wide analyses revealed that YAP inhibits the cardiac maturation transcription factor MEF2A (myocyte-specific enhancer factor 2A), resulting in decreased gene expression of cardiomyocyte maturity pathways. Given the role of MEF2A in regulating contractility, energy production, and mitochondrial homeostasis, we found that perturbing MEF2A transcriptional activity can serve as a strategy to interrupt the cardiomyocyte maturation program and restore the regenerative capacity of the heart.
conclusionsOur research endeavors to provide a comprehensive understanding of the balance of cardiomyocyte metabolic maturation and proliferation to overcome barriers to heart regeneration, offering novel insights into the potential for therapeutic intervention in heart failure.
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