Mineralocorticoid Receptor-Dependent Adverse Remodeling After Myocardial Infarction Mediated by uNGALant Activation of NFκB
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Adverse cardiac healing and remodeling after myocardial infarction (MI) continues to be a major cause of heart failure with reduced ejection fraction.1,2 Primary percutaneous coronary intervention, standard drug treatment, and implantable cardioverter defibrillators improve short- and long-term prognosis post-MI. However, increased survival of patients who have experienced large MIs contributes to high rates of rehospitalization among patients with chronic heart failure with reduced ejection fraction. Thus, novel therapeutic targets to improve left ventricular (LV) healing and remodeling post-MI are needed. In addition to β-blockade and angiotensin-converting enzyme inhibition, early mineralocorticoid receptor (MR) antagonism is indicated for patients who have experienced MI complicated by heart failure or diabetes mellitus.3 Data from rodents demonstrated additive effects of eplerenone and angiotensin-converting enzyme inhibition, with further attenuation of end-diastolic pressures and volumes and significantly improved LV function. In parallel, reactive collagen accumulation in the noninfarcted LV myocardium was prevented by combined angiotensin-converting enzyme inhibition and MR antagonism.4 Furthermore, key evidence for the pivotal role of cardiac MR activation in LV remodeling post-MI comes from rodent studies. These studies suggest that cardiomyocyte-specific deletion of the MR gene attenuated LV dilatation, hypertrophy, fibrosis, and failure after MI in mice, whereas cardiomyocyte-specific MR overexpression induced adverse ventricular remodeling and proarrhythmogenic effects.1,5