ArticleCirculation2020
Pkm2 Regulates Cardiomyocyte Cell Cycle and Promotes Cardiac Regeneration.
Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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Who cites it
192 citing papers in PubMed, 274 citations in OpenAlex.
- Bidirectional metabolic-vascular feedback loops in heart failure: From myocardial energetics to multisystem cardiometabolic crosstalk.iScience · 2026Review
- Pentose phosphate pathway-derived NADPH facilitates physiological hypertrophy and alleviates ischemia-reperfusion injury in the heart.Nature metabolism · 2026Article
- Activation of Glucose-6-Phosphate Dehydrogenase Promotes Cardiomyocyte Cell Cycle.Circulation · 2026Article
- Maternal Exercise and Offspring Cardiac Regenerative Potential: Roles of Apelin and α-Ketoglutarate.Biology · 2026Review
- Small-molecule cocktail 2SM promotes heart regeneration via inducing embryonic-like cardiomyocyte state.Cell regeneration (London, England) · 2026Article
- Cardiac immunity and heart repair: Mechanism, challenge, and future direction.Chinese medical journal · 2026Review
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Photobiomodulation-reprogrammed extracellular vesicles deliveredActa pharmaceutica Sinica. B · 2026Article
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases.Cardiovascular drugs and therapy · 2026Review
- Current Progress and Future Outlook for Synthetic Gene Circuits in Cardiovascular Therapy.Biomolecules · 2026Review
- Nanomicelle-Based Multi-mRNA Delivery Promotes Cardiac Repair After Myocardial Infarction.Small science · 2026Article
- Article
- YAP Induces a Prorenewal Metabolic State in Cardiomyocytes.Circulation · 2026Article
- Retinol saturase in the mitochondria antagonizes IDH2 and GLUD1 acetylation to mediate heart repair.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PHGDH Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via TGF-β/Smad Signalling Pathway.Cell proliferation · 2026Article
- mRNA medicine for cardiovascular disease.Nature cardiovascular research · 2026Review
- Rejuvenating the damaged and aged heart: lessons from development.npj biomedical innovations · 2026Review
132 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 5 countries.
Funding
Abstract
backgroundThe adult mammalian heart has limited regenerative capacity, mostly attributable to postnatal cardiomyocyte cell cycle arrest. In the last 2 decades, numerous studies have explored cardiomyocyte cell cycle regulatory mechanisms to enhance myocardial regeneration after myocardial infarction. Pkm2 (Pyruvate kinase muscle isoenzyme 2) is an isoenzyme of the glycolytic enzyme pyruvate kinase. The role of Pkm2 in cardiomyocyte proliferation, heart development, and cardiac regeneration is unknown.
methodsWe investigated the effect of Pkm2 in cardiomyocytes through models of loss (cardiomyocyte-specific Pkm2 deletion during cardiac development) or gain using cardiomyocyte-specific Pkm2 modified mRNA to evaluate Pkm2 function and regenerative affects after acute or chronic myocardial infarction in mice.
resultsHere, we identify Pkm2 as an important regulator of the cardiomyocyte cell cycle. We show that Pkm2 is expressed in cardiomyocytes during development and immediately after birth but not during adulthood. Loss of function studies show that cardiomyocyte-specific Pkm2 deletion during cardiac development resulted in significantly reduced cardiomyocyte cell cycle, cardiomyocyte numbers, and myocardial size. In addition, using cardiomyocyte-specific Pkm2 modified RNA, our novel cardiomyocyte-targeted strategy, after acute or chronic myocardial infarction, resulted in increased cardiomyocyte cell division, enhanced cardiac function, and improved long-term survival. We mechanistically show that Pkm2 regulates the cardiomyocyte cell cycle and reduces oxidative stress damage through anabolic pathways and β-catenin.
conclusionsWe demonstrate that Pkm2 is an important intrinsic regulator of the cardiomyocyte cell cycle and oxidative stress, and highlight its therapeutic potential using cardiomyocyte-specific Pkm2 modified RNA as a gene delivery platform.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.