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α-Ketoglutarate promotes cardiomyocyte proliferation and heart regeneration after myocardial infarction.
Shi, Yu; Tian, Miao; Zhao, Xiaofang; Tang, Luxun; Wang, Feng; Wu, Hao; Liao, Qiao; Ren, Hongmei; Fu, Wenbin; Zheng, Shuo; Jose, Pedro A; Li, Liangpeng; Zeng, Chunyu.
Afiliación
  • Shi Y; Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.
  • Tian M; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing, P. R. China.
  • Zhao X; Chongqing Key Laboratory for Hypertension Research, Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, P. R. China.
  • Tang L; Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.
  • Wang F; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing, P. R. China.
  • Wu H; Chongqing Key Laboratory for Hypertension Research, Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, P. R. China.
  • Liao Q; Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.
  • Ren H; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing, P. R. China.
  • Fu W; Chongqing Key Laboratory for Hypertension Research, Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, P. R. China.
  • Zheng S; Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.
  • Jose PA; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing, P. R. China.
  • Li L; Chongqing Key Laboratory for Hypertension Research, Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, P. R. China.
  • Zeng C; Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.
Nat Cardiovasc Res ; 3(9): 1083-1097, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39223390
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Miocitos Cardíacos / Proliferación Celular / Histona Demetilasas con Dominio de Jumonji / Ácidos Cetoglutáricos / Infarto del Miocardio Límite: Animals Idioma: En Revista: Nat Cardiovasc Res Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Miocitos Cardíacos / Proliferación Celular / Histona Demetilasas con Dominio de Jumonji / Ácidos Cetoglutáricos / Infarto del Miocardio Límite: Animals Idioma: En Revista: Nat Cardiovasc Res Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido