Nguyen Daniel C, Wells Collin K, Taylor Madison S, Martinez-Ondaro Yania, Singhal Richa, Brittian Kenneth R, Brainard Robert E, Moore Joseph B, Hill Bradford G
Center for Cardiometabolic Science, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine University of Louisville Louisville KY USA.
Department of Physiology University of Louisville Louisville KY USA.
J Am Heart Assoc. 2025 Feb 18;14(4):e037637. doi: 10.1161/JAHA.124.037637. Epub 2025 Feb 14.
Branched-chain amino acids (BCAAs), which are derived from the diet, are markedly elevated in cardiac tissue following myocardial infarction (MI). Nevertheless, it remains unclear whether dietary BCAA levels influence post-MI remodeling.
To investigate the impact of dietary BCAAs on cardiac remodeling and function after MI, we fed mice a low or a high BCAA diet for 2 weeks before MI and for 4 weeks after MI. Cardiac structural and functional changes were evaluated by echocardiography, gravimetry, and histopathological analyses. Immunoblotting was used to evaluate the effects of BCAAs on isolated cardiac myofibroblast differentiation.
The low BCAA diet decreased circulating BCAA concentrations by >2-fold when compared with the high BCAA diet. Although neither body weights nor heart masses were different in female mice fed the custom diets, male mice fed the high BCAA diet had significantly higher body and heart masses than those on the low BCAA diet. The low BCAA diet preserved stroke volume and cardiac output after MI, whereas the high BCAA diet promoted progressive decreases in cardiac function. Although BCAAs were required for myofibroblast differentiation in vitro, cardiac fibrosis, scar collagen topography, and cardiomyocyte cross-sectional area were not different between the dietary groups; however, male mice fed the high BCAA diet had longer cardiomyocytes and higher capillary density compared with the low BCAA group.
A low BCAA diet mitigates eccentric cardiomyocyte remodeling and loss of cardiac function after MI in mice, with dietary effects more prominent in males.
源自饮食的支链氨基酸(BCAAs)在心肌梗死(MI)后心脏组织中显著升高。然而,饮食中BCAAs水平是否影响MI后重塑仍不清楚。
为了研究饮食中BCAAs对MI后心脏重塑和功能的影响,我们在MI前2周和MI后4周给小鼠喂食低BCAA或高BCAA饮食。通过超声心动图、重量测定和组织病理学分析评估心脏结构和功能变化。采用免疫印迹法评估BCAAs对分离的心脏成肌纤维细胞分化的影响。
与高BCAA饮食相比,低BCAA饮食使循环中BCAA浓度降低了2倍以上。尽管喂食定制饮食的雌性小鼠体重和心脏重量没有差异,但喂食高BCAA饮食的雄性小鼠的体重和心脏重量显著高于低BCAA饮食组。低BCAA饮食在MI后保留了每搏输出量和心输出量,而高BCAA饮食促进了心脏功能的逐渐下降。尽管体外成肌纤维细胞分化需要BCAAs,但饮食组之间心脏纤维化、瘢痕胶原形态和心肌细胞横截面积没有差异;然而,与低BCAA组相比,喂食高BCAA饮食的雄性小鼠心肌细胞更长,毛细血管密度更高。
低BCAA饮食可减轻小鼠MI后离心性心肌细胞重塑和心脏功能丧失,饮食对雄性的影响更显著。