title: Mineralocorticoid receptors in vascular disease: connecting molecular pathways to clinical implications.
abstract: The mineralocorticoid receptor (MR), a steroid-hormone-activated transcription factor, plays a substantial role in cardiovascular diseases. MR antagonists (MRAs) have long been appreciated as effective treatments for heart failure and hypertension; however, recent research suggests that additional patient populations may also benefit from MRA therapy. Experimental evidence demonstrates that in addition to its classic role in the regulating sodium handling in the kidney, functional MR is expressed in the blood vessels and contributes to hypertension, vascular inflammation and remodeling, and atherogenesis. MR activation drives pathological phenotypes in smooth muscle cells, endothelial cells, and inflammatory cells, whereas MRAs inhibit these effects. Collectively, these studies demonstrate a new role for extrarenal MR in cardiovascular disease. This review summarizes these new lines of evidence and how they contribute to the mechanisms of atherosclerosis, pulmonary and systemic hypertension, and vein graft failure, and describes new patient populations that may benefit from MRA therapy.
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, 800 Washington Street, Boston, MA, USA. amcgraw@tuftsmedicalcenter.org
authors.forename: Adam P
authors.initials: AP
authors.lastname: McGraw
authors.forename: Amy
authors.initials: A
authors.lastname: McCurley
authors.forename: Ioana R
authors.initials: IR
authors.lastname: Preston
authors.forename: Iris Z
authors.initials: IZ
authors.lastname: Jaffe
mesh_terms: D000450:Aldosterone / Q000627:therapeutic use; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000473:pathology; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D014652:Vascular Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D014680:Veins / Q000637:transplantation
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone