Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Metabolism. 2013 Feb;62(2):290-302. doi: 10.1016/j.metabol.2012.07.023. Epub 2012 Aug 28.
Evidence suggests that branched chain amino acids (BCAAs) are beneficial in treating human disease. It is unknown, however, what impact BCAAs have on outcomes in acute myocardial infarction (MI). This study was performed to test the hypothesis that the specific BCAA leucine mitigates cardiac injury and improves survival post-MI.
MATERIALS/METHODS: 11-12 week old male C57BL/6 mice were subjected to experimental MI or sham procedure, and provided regular chow (RC; 1.5% leucine) or a high leucine diet (HLD; 5% leucine), and followed for 3½ or 28 days. All mice were studied by echocardiography and cardiac catheterization, and all hearts were collected for histologic measurements of hypertrophy, fibrosis and apoptosis. Inflammation, hypertrophic gene expression, signal transduction, and glucose, palmitate and leucine metabolism were also measured in 3½day hearts.
Except for increased leucine and decreased glucose oxidation, an HLD had no effect on measured outcomes in sham mice. With MI, cardiac structure, function, and survival were significantly improved with an HLD. At 3½days post-MI, an HLD increased cardiac hypertrophic signaling and decreased inflammation. Cardiac leucine oxidation was decreased in RC mice post-MI, but significantly increased with an HLD. These changes in metabolism were accompanied by a significant increase in cardiac ATP content in the HLD group. Finally, at both 3½ and 28 days post-MI, an HLD increased compensatory hypertrophy, and attenuated cardiac fibrosis and apoptosis.
An HLD increases compensatory hypertrophy, attenuates fibrosis and apoptosis, and positively modulates oxidative metabolism to improve cardiac structure, function, and survival post-MI.
有证据表明支链氨基酸（BCAAs）有益于治疗人类疾病。然而，尚不清楚 BCAAs 对急性心肌梗死（MI）的结局有何影响。本研究旨在验证以下假设：特定的支链氨基酸亮氨酸可减轻心脏损伤并改善 MI 后生存。
材料/方法：11-12 周龄雄性 C57BL/6 小鼠接受实验性 MI 或假手术处理，并给予常规饮食（RC；1.5%亮氨酸）或高亮氨酸饮食（HLD；5%亮氨酸），并随访 3 天半或 28 天。所有小鼠均进行超声心动图和心导管检查，并收集所有心脏进行组织学测量，以评估肥大、纤维化和细胞凋亡。炎症、肥大基因表达、信号转导以及葡萄糖、棕榈酸和亮氨酸代谢也在 3 天半的心脏中进行了测量。
除了亮氨酸增加和葡萄糖氧化减少外，HLD 对假手术小鼠的所有测量结果均无影响。在 MI 中，HLD 可显著改善心脏结构、功能和生存。在 MI 后 3 天半，HLD 增加了心脏肥大信号并减少了炎症。MI 后 RC 小鼠的心脏亮氨酸氧化减少，但 HLD 组显著增加。代谢的这些变化伴随着 HLD 组心脏 ATP 含量的显著增加。最后，在 MI 后 3 天半和 28 天，HLD 增加了代偿性肥大，减轻了心脏纤维化和细胞凋亡。
HLD 可增加代偿性肥大，减轻纤维化和细胞凋亡，并积极调节氧化代谢，以改善 MI 后心脏结构、功能和生存。
