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Article

Letrozole Accelerates Metabolic Remodeling through Activation of Glycolysis in Cardiomyocytes: A Role beyond Hormone Regulation

1
College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea
2
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
*
Author to whom correspondence should be addressed.
Academic Editors: Demetrios A. Arvanitis and Anastasios Lymperopoulos
Int. J. Mol. Sci. 2022, 23(1), 547; https://doi.org/10.3390/ijms23010547
Received: 30 November 2021 / Revised: 23 December 2021 / Accepted: 1 January 2022 / Published: 4 January 2022
Estrogen receptor-positive (ER+) breast cancer patients are recommended hormone therapy as a primary adjuvant treatment after surgery. Aromatase inhibitors (AIs) are widely administered to ER+ breast cancer patients as estrogen blockers; however, their safety remains controversial. The use of letrozole, an AI, has been reported to cause adverse cardiovascular effects. We aimed to elucidate the effects of letrozole on the cardiovascular system. Female rats exposed to letrozole for four weeks showed metabolic changes, i.e., decreased fatty acid oxidation, increased glycolysis, and hypertrophy in the left ventricle. Although lipid oxidation yields more ATP than carbohydrate metabolism, the latter predominates in the heart under pathological conditions. Reduced lipid metabolism is attributed to reduced β-oxidation due to low circulating estrogen levels. In letrozole-treated rats, glycolysis levels were found to be increased in the heart. Furthermore, the levels of glycolytic enzymes were increased (in a high glucose medium) and the glycolytic rate was increased in vitro (H9c2 cells); the same was not true in the case of estrogen treatment. Reduced lipid metabolism and increased glycolysis can lower energy supply to the heart, resulting in predisposition to heart failure. These data suggest that a letrozole-induced cardiac metabolic remodeling, i.e., a shift from β-oxidation to glycolysis, may induce cardiac structural remodeling. View Full-Text
Keywords: letrozole; β-oxidation; glycolysis; cardiac hypertrophy letrozole; β-oxidation; glycolysis; cardiac hypertrophy
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MDPI and ACS Style

Heo, J.H.; Lee, S.R.; Jo, S.L.; Yang, H.; Lee, H.W.; Hong, E.-J. Letrozole Accelerates Metabolic Remodeling through Activation of Glycolysis in Cardiomyocytes: A Role beyond Hormone Regulation. Int. J. Mol. Sci. 2022, 23, 547. https://doi.org/10.3390/ijms23010547

AMA Style

Heo JH, Lee SR, Jo SL, Yang H, Lee HW, Hong E-J. Letrozole Accelerates Metabolic Remodeling through Activation of Glycolysis in Cardiomyocytes: A Role beyond Hormone Regulation. International Journal of Molecular Sciences. 2022; 23(1):547. https://doi.org/10.3390/ijms23010547

Chicago/Turabian Style

Heo, Jun H., Sang R. Lee, Seong Lae Jo, Hyun Yang, Hye Won Lee, and Eui-Ju Hong. 2022. "Letrozole Accelerates Metabolic Remodeling through Activation of Glycolysis in Cardiomyocytes: A Role beyond Hormone Regulation" International Journal of Molecular Sciences 23, no. 1: 547. https://doi.org/10.3390/ijms23010547

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