Role of Mast Cells in Cardiovascular Disease

Abstract

Increased numbers of mast cells have been reported in human hearts with end-stage cardiomyopathy and in animal models of myocardial infarction, hypertension, and chronic volume overload secondary to mitral regurgitation and aortocaval fistula. Because of these observations, mast cells have been implicated in the pathophysiology of these cardiovascular disorders. Mast cells are known to store and release a variety of biologically active mediators, including numerous cytokines (e.g.,TNF-α and IL-6) and proteases (e.g., tryptase, chymase, and stromelysin), many of which are potentially involved in activating matrix metalloproteinases (MMPs). Accordingly, in this review, the potential role of cardiac mast cells in MMP activation, thereby causing fibrillar collagen degradation and adverse cardiac remodeling is considered. In particular, the following topics are contemplated: 1) the origin of increased cardiac mast cell density; 2) the functional consequences of cardiac mast cell degranulation; 3) the relationship between mast cell density and MMP activity; 4) the contribution of mast cell derived TNF-α to myocardial remodeling; 5) the effect of pharmacological prevention of mast cell degranulation on myocardial remodeling; 6) the effect of mast cells on fibroblast function; 7) a possible role of atrial natriuretic peptide in initiating the mast cell-MMP activation cascade; and 8) future research questions.Key wordsCompound 48/80Matrix Metalloproteinase ActivityVentricular DilatationMyocardial RemodelingCytokines