title: Cardiac mast cells: the centrepiece in adverse myocardial remodelling.
abstract: Increased numbers of mast cells have been reported in explanted human hearts with dilated cardiomyopathy and in animal models of experimentally induced hypertension, myocardial infarction, and chronic volume overload secondary to aortocaval fistula and mitral regurgitation. Accordingly, mast cells have been implicated to have a major role in the pathophysiology of these cardiovascular disorders. In vitro studies have verified that mast cell proteases are capable of activating collagenase, gelatinases and stromelysin. Recent results have shown that with chronic ventricular volume overload, there is an elevation in mast cell density, which is associated with a concomitant increase in matrix metalloproteinase (MMP) activity and extracellular matrix degradation. However, the role of the cardiac mast cell is not one dimensional, with evidence from hypertension and cardiac transplantation studies suggesting that they can also assume a pro-fibrotic phenotype in the heart. These adverse events do not occur in mast cell deficient rodents or when cardiac mast cells are pharmacologically prevented from degranulating. This review is focused on the regulation and dual roles of cardiac mast cells in: (i) activating MMPs and causing myocardial fibrillar collagen degradation and (ii) causing fibrosis in the stressed, injured or diseased heart. Moreover, there is strong evidence that premenopausal female cardioprotection may at least partly be due to gender differences in cardiac mast cells. This too will be addressed.
authors.affiliation: Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Levick
authors.forename: Giselle C
authors.initials: GC
authors.lastname: Meléndez
authors.forename: Eric
authors.initials: E
authors.lastname: Plante
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McLarty
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Brower
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Janicki
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000473:pathology* / Q000503:physiopathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D015936:Complement C5a / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000473:pathology* / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D009205:Myocarditis / Q000473:pathology / Q000503:physiopathology; D009479:Neuropeptides / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012727:Sex Characteristics; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D019332:Endothelin-1; D009479:Neuropeptides; D017382:Reactive Oxygen Species; D015936:Complement C5a