The mammalian heart contains a resident population of mast cells, strategically located around vessels. Myocardial ischemia triggers rapid degranulation of cardiac mast cells through pathways that may involve complement activation, adenosine signaling and generation of reactive oxygen species. Release of pro-inflammatory mast cell-derived mediators, such as histamine, tryptase, chymase, and Tumor Necrosis Factor (TNF)- initiates the cytokine cascade, ultimately leading to infiltration of the infarcted heart with leukocytes. During the proliferative phase of healing, Stem Cell Factor (SCF) is induced in the infarct and promotes recruitment of mast cell progenitors, leading to a significant increase in mast cell density. Through their ability to secrete large amounts of pro-fibrotic and angiogenic mediators, such as Transforming Growth Factor (TGF)-, basic Fibroblast Growth Factor, tryptase and chymase, mast cells may actively participate in the reparative response. In addition, mast cells may contribute to extracellular matrix metabolism by producing and releasing matrix metalloproteinases. Because of the diversity of their secretory products and their phenotypic and functional heterogeneity, mast cells may exert both protective and detrimental actions on the infarcted and remodeling heart. Although some experimental evidence suggests beneficial effects of mast cell stabilization in models of cardiac injury, targeting unique mast cell-derived mediators (such as histamine, chymase and tryptase) may represent a more specific and mechanism-oriented therapeutic strategy.
|Original language||English (US)|
|Title of host publication||Mast Cells and Cardiovascular Disease|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||16|
|Publication status||Published - Jan 1 2010|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)