Abstract

Myocardial infarction (MI) induces extensive structural and metabolic remodeling; however, many metabolic pathways have not been evaluated. Therefore, we performed a comprehensive analysis of the metabolites that are altered during heart failure. We induced heart failure in mice via surgically occluding the left coronary artery and evaluated ventricular function with echocardiography. We found a significant (p<0.05) difference in 87 out of 288 measured metabolites five days after MI. Interestingly, MI significantly (p<0.05) increased branched chain amino acids (BCAAs), including Valine, Leucine, and Isoleucine. Linear regression analysis showed a negative relationship between ejection fraction and the BCAA abundance (Figure panels A, B, and C). In addition, the polyamines putrescine and spermidine – which are associated with the fibrotic response and provide a level of internal contextualization of the present results with previous studies – showed a negative relationship between ejection fraction and polyamine levels in the heart (Figure panels D and E). As expected, many metabolites change during heart failure and the present results suggest a heretofore-unexplored relationship between BCAAs and the severity of heart failure. Grant Funding Source: Supported by the NIH and AHA

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