title: Mineralocorticoids in the heart and vasculature: new insights for old hormones.
abstract: The mineralocorticoid aldosterone is a key regulator of water and electrolyte homeostasis. Numerous recent developments have advanced the field of mineralocorticoid pharmacology—namely, clinical trials have shown the beneficial effects of aldosterone antagonists in chronic heart failure and post-myocardial infarction treatment. Experimental studies using cell type-specific gene targeting of the mineralocorticoid receptor (MR) gene in mice have revealed the importance of extrarenal aldosterone signaling in cardiac myocytes, endothelial cells, vascular smooth cells, and macrophages. In addition, several molecular pathways involving signal transduction via the classical MR as well as the G protein-coupled receptor GPER mediate the diverse spectrum of effects of aldosterone on cells. This knowledge has initiated the development of new pharmacological ligands to specifically interfere with targets on different levels of aldosterone signaling. For example, aldosterone synthase inhibitors such as LCI699 and the novel nonsteroidal MR antagonist BAY 94-8862 have been tested in clinical trials. Interference with the interaction between MR and its coregulators seems to be a promising strategy toward the development of selective MR modulators.
authors.affiliation: Heart Center, Department of Cardiology and Angiology I, University of Freiburg, 79106 Freiburg, Germany; email: achim.lother@universitaets-herzzentrum.de.
authors.forename: Achim
authors.initials: A
authors.lastname: Lother
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Ross D
authors.initials: RD
authors.lastname: Feldman
authors.forename: Lutz
authors.initials: L
authors.lastname: Hein
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone
keywords: aldosterone; aldosterone antagonists; cardiovascular system; mineralocorticoid receptor; nuclear receptor