Anca Kliesow Remes,Theresa Ruf,Tinatin Zurashvili,Lin Ding,Moritz Meyer-Jens,Dominic M Schwab,Susanne Hille,Andrea Matzen,Sabine Michalewski,Lucia Kilian,Prithviraj Manohar Vijaya Shetty,Marie-Christin Fuchs,Matthias Eden,Hermann-Josef Gröne,Kleopatra Rapti,Andreas Jungmann,Hendrik Milting,Hugo A Katus,Lucie Carrier,Derk Frank,Norbert Frey,Oliver J Müller
{"title":"在小鼠压力过载模型中,aav介导的CPT1B过表达可防止心脏肥厚和心力衰竭。","authors":"Anca Kliesow Remes,Theresa Ruf,Tinatin Zurashvili,Lin Ding,Moritz Meyer-Jens,Dominic M Schwab,Susanne Hille,Andrea Matzen,Sabine Michalewski,Lucia Kilian,Prithviraj Manohar Vijaya Shetty,Marie-Christin Fuchs,Matthias Eden,Hermann-Josef Gröne,Kleopatra Rapti,Andreas Jungmann,Hendrik Milting,Hugo A Katus,Lucie Carrier,Derk Frank,Norbert Frey,Oliver J Müller","doi":"10.1007/s00395-025-01123-y","DOIUrl":null,"url":null,"abstract":"The transition from cardiac hypertrophy to heart failure is characterized by metabolic changes like downregulation of fatty acid metabolism in favor of increased glucose utilization. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of the carnitine shuttle and is an essential enzyme for fatty acid oxidation. Down-regulation of CPT1B activity has been associated with heart failure in patients and various experimental models, indicating an important role in metabolic remodeling. Therefore, we aimed to investigate whether CPT1B overexpression could play a therapeutic role in heart failure. Gene transfer of CPT1B using adeno-associated virus (AAV) vectors into neonatal rat cardiomyocytes significantly attenuated phenylephrine-induced hypertrophy and resulted in decreased generation of mitochondrial reactive oxygen species. In mice subjected to transverse aortic constriction, AAV-mediated cardiac overexpression of CPT1B attenuated cardiomyocyte hypertrophy, cardiac fibrosis, and systolic dysfunction in vivo. Upregulation of CPT1B expression might therefore represent a promising approach to treat or prevent heart failure.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"44 1","pages":""},"PeriodicalIF":8.0000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"AAV-mediated overexpression of CPT1B protects from cardiac hypertrophy and heart failure in a murine pressure overload model.\",\"authors\":\"Anca Kliesow Remes,Theresa Ruf,Tinatin Zurashvili,Lin Ding,Moritz Meyer-Jens,Dominic M Schwab,Susanne Hille,Andrea Matzen,Sabine Michalewski,Lucia Kilian,Prithviraj Manohar Vijaya Shetty,Marie-Christin Fuchs,Matthias Eden,Hermann-Josef Gröne,Kleopatra Rapti,Andreas Jungmann,Hendrik Milting,Hugo A Katus,Lucie Carrier,Derk Frank,Norbert Frey,Oliver J Müller\",\"doi\":\"10.1007/s00395-025-01123-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The transition from cardiac hypertrophy to heart failure is characterized by metabolic changes like downregulation of fatty acid metabolism in favor of increased glucose utilization. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of the carnitine shuttle and is an essential enzyme for fatty acid oxidation. Down-regulation of CPT1B activity has been associated with heart failure in patients and various experimental models, indicating an important role in metabolic remodeling. Therefore, we aimed to investigate whether CPT1B overexpression could play a therapeutic role in heart failure. Gene transfer of CPT1B using adeno-associated virus (AAV) vectors into neonatal rat cardiomyocytes significantly attenuated phenylephrine-induced hypertrophy and resulted in decreased generation of mitochondrial reactive oxygen species. In mice subjected to transverse aortic constriction, AAV-mediated cardiac overexpression of CPT1B attenuated cardiomyocyte hypertrophy, cardiac fibrosis, and systolic dysfunction in vivo. Upregulation of CPT1B expression might therefore represent a promising approach to treat or prevent heart failure.\",\"PeriodicalId\":8723,\"journal\":{\"name\":\"Basic Research in Cardiology\",\"volume\":\"44 1\",\"pages\":\"\"},\"PeriodicalIF\":8.0000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Basic Research in Cardiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00395-025-01123-y\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Basic Research in Cardiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00395-025-01123-y","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
AAV-mediated overexpression of CPT1B protects from cardiac hypertrophy and heart failure in a murine pressure overload model.
The transition from cardiac hypertrophy to heart failure is characterized by metabolic changes like downregulation of fatty acid metabolism in favor of increased glucose utilization. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of the carnitine shuttle and is an essential enzyme for fatty acid oxidation. Down-regulation of CPT1B activity has been associated with heart failure in patients and various experimental models, indicating an important role in metabolic remodeling. Therefore, we aimed to investigate whether CPT1B overexpression could play a therapeutic role in heart failure. Gene transfer of CPT1B using adeno-associated virus (AAV) vectors into neonatal rat cardiomyocytes significantly attenuated phenylephrine-induced hypertrophy and resulted in decreased generation of mitochondrial reactive oxygen species. In mice subjected to transverse aortic constriction, AAV-mediated cardiac overexpression of CPT1B attenuated cardiomyocyte hypertrophy, cardiac fibrosis, and systolic dysfunction in vivo. Upregulation of CPT1B expression might therefore represent a promising approach to treat or prevent heart failure.
期刊介绍:
Basic Research in Cardiology is an international journal for cardiovascular research. It provides a forum for original and review articles related to experimental cardiology that meet its stringent scientific standards.
Basic Research in Cardiology regularly receives articles from the fields of
- Molecular and Cellular Biology
- Biochemistry
- Biophysics
- Pharmacology
- Physiology and Pathology
- Clinical Cardiology