Reversal of metabolic shift in post-infarct-remodelled hearts: possible novel therapeutic approach

Abstract

This editorial refers to ‘Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury’ by P.-H. Lou et al ., doi:10.1093/cvr/cvs323. With sophistication and improvement in coronary revascularization therapy, the chances of patients surviving acute myocardial infarction have been increasing. Though the procedure is life-saving, it also predisposes the patients to post-infarction ventricular remodelling and consequent heart failure. Since those patients usually have atherosclerotic lesions not only in the culprit vessel in the infarction but also in some part of the coronary artery, the likelihood of them having re-infarction is substantial. The mortality of patients with re-infarction has been reported to be more than twice as high as that by the first attack,1 probably due, at least in part, to disrupted intrinsic cardioprotective signalling in post-infarct-remodelled hearts.2 In addition to the change in intracellular signal transduction, it has been well established that a so-called metabolic shift takes place as cardiac hypertrophy and heart failure develop. In healthy hearts, oxidation of fatty acids (FAs) covers >70% of the cardiac energy need, with most of the remainder being accounted for by glucose oxidation.3 On the other hand, hearts change their substrate preference from FAs towards glucose as remodelling develops in response to diverse stresses.3 The oxidation of one molecule of FAs yields far more ATP (∼129 ATP in the case of palmitate) than glucose (∼36 ATP). Therefore, glucose oxidation can hardly compensate for the decrease in ATP synthesis when the oxidation of FAs …