Basic research in cardiology · 2025
AAV-mediated overexpression of CPT1B protects from cardiac hypertrophy and heart failure in a murine pressure overload model.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Kliesow Remes Anca, Ruf Theresa, Zurashvili Tinatin, Ding Lin, Meyer-Jens Moritz, Schwab Dominic M, Hille Susanne, Matzen Andrea, Michalewski Sabine, Kilian Lucia, Shetty Prithviraj Manohar Vijaya, Fuchs Marie-Christin, Eden Matthias, Gröne Hermann-Josef, Rapti Kleopatra, Jungmann Andreas, Milting Hendrik, Katus Hugo A, Carrier Lucie, Frank Derk, Frey Norbert, Müller Oliver J
Аннотация
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.