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
Department of Internal Medicine V, University of Kiel, Kiel, Germany.
German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Kiel, Germany.
Basic Res Cardiol. 2025 Jul 11. doi: 10.1007/s00395-025-01123-y.
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.
从心脏肥大到心力衰竭的转变，其特征是代谢变化，如脂肪酸代谢下调，转而增加葡萄糖利用。肉碱棕榈酰转移酶1B（CPT1B）催化肉碱穿梭的限速步骤，是脂肪酸氧化的关键酶。CPT1B活性下调与患者及各种实验模型中的心力衰竭相关，表明其在代谢重塑中起重要作用。因此，我们旨在研究CPT1B过表达是否能在心力衰竭中发挥治疗作用。使用腺相关病毒（AAV）载体将CPT1B基因导入新生大鼠心肌细胞，可显著减轻去氧肾上腺素诱导的肥大，并减少线粒体活性氧的产生。在接受主动脉缩窄的小鼠中，AAV介导的CPT1B心脏过表达可减轻体内心肌细胞肥大、心脏纤维化和收缩功能障碍。因此，上调CPT1B表达可能是治疗或预防心力衰竭的一种有前景的方法。
