title: Renin: at the heart of the mast cell.
abstract: Cardiac mast cells proliferate in cardiovascular diseases. In myocardial ischemia, mast cell mediators contribute to coronary vasoconstriction, arrhythmias, leukocyte recruitment, and tissue injury and repair. Arrhythmic dysfunction, coronary vasoconstriction, and contractile failure are also characteristic of cardiac anaphylaxis. In coronary atherosclerosis, mast cell mediators facilitate cholesterol accumulation and plaque destabilization. In cardiac failure, mast cell chymase causes myocyte apoptosis and fibroblast proliferation, leading to ventricular dysfunction. Chymase and tryptase also contribute to fibrosis in cardiomyopathies and myocarditis. In addition, mast cell tumor necrosis factor-alpha promotes myocardial remodeling. Cardiac remodeling and hypertrophy in end-stage hypertension are also induced by mast cell mediators and proteases. We recently discovered that cardiac mast cells contain and release renin, which initiates local angiotensin formation. Angiotensin causes coronary vasoconstriction, arrhythmias, fibrosis, apoptosis, and endothelin release, all demonstrated mechanisms of mast-cell-associated cardiac disease. The effects of angiotensin are further amplified by the release of norepinephrine from cardiac sympathetic nerves. Our discovery of renin in cardiac mast cells and its release in pathophysiological conditions uncovers an important new pathway in the development of mast-cell-associated heart diseases. Several steps in this novel pathway may constitute future therapeutic targets.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Alicia C
authors.initials: AC
authors.lastname: Reid
authors.forename: Randi B
authors.initials: RB
authors.lastname: Silver
authors.forename: Roberto
authors.initials: R
authors.lastname: Levi
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000276:immunology; D006321:Heart; D006801:Humans; D008407:Mast Cells / Q000276:immunology*; D009206:Myocardium / Q000276:immunology*; D012083:Renin / Q000378:metabolism*
chemical_list: D012083:Renin