Abstract 4141547: Dietary Branched Chain Amino Acids Modify Post-Infarct Cardiac Remodeling and Function in the Murine Heart

Introduction: Branched chain amino acids (BCAAs) are essential amino acids that are elevated in the failing heart and that have been linked with cardiovascular disease risk. Yet, it remains unclear how BCAAs influence the heart after injury. In this study, we examined in mice whether dietary alterations of BCAA levels influences cardiac structure and function after myocardial infarction (MI). Methods and Results: To assess whether altering dietary BCAA levels would impact circulating BCAA concentrations, mice were fed a low (1/3×), normal (1×), or high (2×) BCAA diet over a 7-day period. The low and high BCAA diets were matched for macronutrient content, nitrogen content, and caloric density. We found that mice fed the low BCAA diet had >2-fold lower circulating BCAA concentrations when compared with normal and high BCAA diet feeding strategies (n=8/group; p<0.05); notably, the high BCAA diet did not further increase BCAA levels over the normal chow diet. To investigate the impact of dietary BCAAs on cardiac remodeling and function after MI, male and female mice were fed either the low or high BCAA diet for 2 wk prior to MI and for 4 wk after MI. Although body weight (BW) or heart mass (HW/TL) were not different in female mice fed the custom diets, male mice fed the high BCAA diet had higher BW and HW/TL than those on the low BCAA diet (n = 7–10/group; p<0.05). Echocardiography prior to MI (baseline) and at 2- and 4-wk post-MI revealed that the low BCAA diet preserved stroke volume (SV) and cardiac output (CO), whereas mice fed a high BCAA diet showed progressive decreases in SV and CO, which reached statistical significance by 4 wk post-MI (p<0.05). Structural analysis further demonstrated higher LV mass in mice fed the high BCAA diet compared with the low BCAA diet (n = 7–10/group; p<0.05). Although no differences in cardiac fibrosis or cardiomyocyte cross-sectional area were found between the dietary groups, male mice fed the high BCAA diet showed longer cardiomyocytes and higher capillary density compared with the low BCAA gorup (n = 6-10/group; p<0.05). Conclusions: These preclinical results demonstrate that dietary BCAA levels influence cardiac structure and function after MI and suggest that a diet low in BCAAs minimizes deleterious remodeling, especially in male mice.