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. 2025 Oct;120(5):975-989.
doi: 10.1007/s00395-025-01123-y. Epub 2025 Jul 11.

AAV-mediated overexpression of CPT1B protects from cardiac hypertrophy and heart failure in a murine pressure overload model

Anca Kliesow Remes #  1   2 , Theresa Ruf #  3   4 , Tinatin Zurashvili  1   5 , Lin Ding  3   6 , Moritz Meyer-Jens  2   7 , Dominic M Schwab  3 , Susanne Hille  1   2 , Andrea Matzen  2   6 , Sabine Michalewski  1   2 , Lucia Kilian  2   6 , Prithviraj Manohar Vijaya Shetty  1   2 , Marie-Christin Fuchs  3 , Matthias Eden  3   4   6 , Hermann-Josef Gröne  8 , Kleopatra Rapti  3 , Andreas Jungmann  3 , Hendrik Milting  9 , Hugo A Katus  3   4 , Lucie Carrier  2   7 , Derk Frank  2   6 , Norbert Frey  3   4 , Oliver J Müller  10   11
Affiliations

AAV-mediated overexpression of CPT1B protects from cardiac hypertrophy and heart failure in a murine pressure overload model

Anca Kliesow Remes et al. Basic Res Cardiol. 2025 Oct.

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.

Keywords: Adeno-associated virus; CPT1B; Cardiac hypertrophy; Fatty acid metabolism; Heart failure; Metabolic remodeling.

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Conflict of interest statement

Declarations. Conflict of Interest: None. Ethical approval: Animal experiments were executed with approval of the local authorities in Karlsruhe (approval of the Karlsruhe Regional Council 35-9185.81/G-122/12). Human sample collection was approved by the responsible ethics committee (permission numbers D462/15 and D506/22). Consent to participate: Not applicable. Consent for publication: All the authors approved the final manuscript and agreed to publication in Basic Research in Cardiology.

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