DOI: 10.1161/jaha.124.037637 ISSN: 2047-9980

Dietary Branched‐Chain Amino Acids Modify Postinfarct Cardiac Remodeling and Function in the Murine Heart

Daniel C. Nguyen, Collin K. Wells, Madison S. Taylor, Yania Martinez‐Ondaro, Richa Singhal, Kenneth R. Brittian, Robert E. Brainard, Joseph B. Moore, Bradford G. Hill
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Background

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.

Methods

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.

Results

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.

Conclusions

A low BCAA diet mitigates eccentric cardiomyocyte remodeling and loss of cardiac function after MI in mice, with dietary effects more prominent in males.

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