| First Author | Shi Y | Year | 2024 |
| Journal | Nat Cardiovasc Res | Volume | 3 |
| Issue | 9 | Pages | 1083-1097 |
| PubMed ID | 39223390 | Mgi Jnum | J:359069 |
| Mgi Id | MGI:7782848 | Doi | 10.1038/s44161-024-00531-y |
| Citation | Shi Y, et al. (2024) alpha-Ketoglutarate promotes cardiomyocyte proliferation and heart regeneration after myocardial infarction. Nat Cardiovasc Res 3(9):1083-1097 |
| abstractText | 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 alpha-ketoglutarate ranked highest among the decreased metabolites. Injection of alpha-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 alpha-ketoglutarate levels. Mechanistically, alpha-ketoglutarate decreases H3K27me3 deposition at the promoters of cell cycle genes in cardiomyocytes. Thus, alpha-ketoglutarate promotes cardiomyocyte proliferation through JMJD3-dependent demethylation, offering a potential approach for treating myocardial infarction. |
