Restoration of Cardiac Function After Myocardial Infarction by Long-Term Activation of the CNS Leptin-Melanocortin System
Fábio Nelson Gava, Alexandre A. da Silva, Xuemei Dai, Romain Harmancey, Sadia Ashraf, Ana Carolina Mieko Omoto, Mateus C. Salgado, Sydney P. Moak, Xuan Li, John E. Hall, Jussara M. do Carmo
Abstract
Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca2+ coupling, and mitochondrial efficiency. These findings highlight a potentially novel therapeutic approach for myocardial infarction and heart failure.