ArticleNature cardiovascular research2024
α-Ketoglutarate promotes cardiomyocyte proliferation and heart regeneration after myocardial infarction.
Article in Nature cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed.
- Malate-aspartate shuttle inactivation drives pulmonary hypertension through glucose carbon flux rewiring and α-ketoglutarate-dependent epigenetic remodeling.Redox biology · 2026Article
- α-Ketoglutarate accelerates cutaneous wound healing through modulating the epithelial-fibroblast niche.JCI insight · 2026Article
- Loss of the mitochondrial SAM transporter reveals a lipoylation-dependent metabolic vulnerability in the postnatal heart.Science advances · 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
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Urea cycle fumarate limits fibrosis post-myocardial infarction by reducing fibroblast mitochondrial adenosine triphosphate production.Cardiovascular research · 2026Article
- Traditional Chinese Medicine Intervention Based on Metabolic-Epigenetic Axis: Mechanism and Treatment Strategy of Chronic Heart Failure.Biomolecules · 2026Review
- Spatiotemporal reprogramming of cardiac lipid metabolism by platelet-engineered RNA therapy epigenetically modulate heart repair and regeneration.Bioactive materials · 2026Article
- Alpha-ketoglutarate accelerates granulocyte-monocyte progenitor differentiation and atherosclerotic plaque inflammation via oxoglutarate receptor 1.Redox biology · 2026Article
- Spatiotemporal precision interventions for cardiac repair and regenerative therapy.Experimental & molecular medicine · 2026Review
- OGDH mediates α-ketoglutarate-induced follicular development and antioxidative response by interacting with CAT/SOD2.Biological research · 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
- Alpha-Ketoglutarate: A Metabolic Regulator of Cellular Homeostasis and Pathophysiology.Biomedicines · 2026Review
- The Metabolic Role of Mitochondria in the Perinatal Cardiac Development and Cardiovascular Diseases.Exploration (Beijing, China) · 2026Review
- Rejuvenating the damaged and aged heart: lessons from development.npj biomedical innovations · 2026Review
- Article
- An Integrated Evaluation Framework for Adult Heart Regeneration.Journal of cellular and molecular medicine · 2026Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The neonatal mammalian heart can regenerate following injury through cardiomyocyte proliferation but loses this potential by postnatal day 7. Stimulating adult cardiomyocytes to reenter the cell cycle remains unclear. Here we show that cardiomyocyte proliferation depends on its metabolic state. Given the connection between the tricarboxylic acid cycle and cell proliferation, we analyzed these metabolites in mouse hearts from postnatal day 0.5 to day 7 and found that α-ketoglutarate ranked highest among the decreased metabolites. Injection of α-ketoglutarate extended the window of cardiomyocyte proliferation during heart development and promoted heart regeneration after myocardial infarction by inducing adult cardiomyocyte proliferation. This was confirmed in Ogdh-siRNA-treated mice with increased α-ketoglutarate levels. Mechanistically, α-ketoglutarate decreases H3K27me3 deposition at the promoters of cell cycle genes in cardiomyocytes. Thus, α-ketoglutarate promotes cardiomyocyte proliferation through JMJD3-dependent demethylation, offering a potential approach for treating myocardial infarction.
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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.