title: The cardioprotective effects of mineralocorticoid receptor antagonists.
abstract: Despite state-of-the-art reperfusion therapy, morbidity and mortality remain significant in patients with an acute myocardial infarction. Therefore, novel strategies to limit myocardial ischemia-reperfusion injury are urgently needed. Mineralocorticoid receptor (MR) antagonists are attractive candidates for this purpose, since several clinical trials in patients with heart failure have reported a survival benefit with MR antagonist treatment. MRs are expressed by several cells of the cardiovascular system, including cardiomyocytes, cardiac fibroblasts, vascular smooth muscle cells, and endothelial cells. Experiments in animal models of myocardial infarction have demonstrated that acute administration of MR antagonists, either before ischemia or immediately at the moment of coronary reperfusion, limits infarct size. This action appears to be independent of the presence of aldosterone and cortisol, which are the endogenous ligands for the MR. The cardioprotective effect is mediated by a nongenomic intracellular signaling pathway, including adenosine receptor stimulation, and activation of several components of the Reperfusion Injury Salvage Kinase (RISK) pathway. In addition to limiting infarct size, MR antagonists can improve scar healing when administered shortly after reperfusion and can reduce cardiac remodeling post myocardial infarction. Clinical trials are currently being performed studying whether early administration of MR antagonists can indeed improve prognosis in patients with an acute myocardial infarction, independent of the presence of heart failure.
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: T N A
authors.initials: TN
authors.lastname: van den Berg
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
authors.affiliation: The Hatter Cardiovascular Institute, University College London, United Kingdom.
authors.forename: Georg M
authors.initials: GM
authors.lastname: Fröhlich
authors.affiliation: Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Deinum
authors.affiliation: The Hatter Cardiovascular Institute, University College London, United Kingdom.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands. Electronic address: N.Riksen@aig.umcn.nl.
authors.forename: Niels P
authors.initials: NP
authors.lastname: Riksen
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000378:metabolism; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid
keywords: Aldosterone; Antagonist; Cardiac remodeling; Ischemia–reperfusion injury; Mineralocorticoid receptor; Myocardium