Heo Jun H, Lee Sang R, Jo Seong Lae, Yang Hyun, Lee Hye Won, Hong Eui-Ju
College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea.
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.
Int J Mol Sci. 2022 Jan 4;23(1):547. doi: 10.3390/ijms23010547.
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.
雌激素受体阳性（ER+）乳腺癌患者术后推荐接受激素治疗作为主要辅助治疗。芳香化酶抑制剂（AIs）作为雌激素阻滞剂被广泛应用于ER+乳腺癌患者；然而，其安全性仍存在争议。据报道，使用AI来曲唑会引起不良心血管效应。我们旨在阐明来曲唑对心血管系统的影响。暴露于来曲唑四周的雌性大鼠出现了代谢变化，即脂肪酸氧化减少、糖酵解增加以及左心室肥大。尽管脂质氧化比碳水化合物代谢产生更多的三磷酸腺苷（ATP），但在病理条件下，后者在心脏中占主导地位。脂质代谢减少归因于循环雌激素水平低导致的β氧化减少。在接受来曲唑治疗的大鼠中，发现心脏中的糖酵解水平增加。此外，（在高糖培养基中）糖酵解酶水平升高，体外（H9c2细胞）糖酵解速率增加；雌激素治疗的情况则并非如此。脂质代谢减少和糖酵解增加会降低心脏的能量供应，导致易患心力衰竭。这些数据表明，来曲唑诱导的心脏代谢重塑，即从β氧化向糖酵解的转变，可能会诱导心脏结构重塑。
