Abstract
Historically, increased numbers of mast cells have been associated with fibrosis in numerous cardiac pathologies, implicating mast cells in the development of cardiac fibrosis. Subsequently, several approaches have been utilised to demonstrate a causal role for mast cells in animal models of cardiac fibrosis including mast cell stabilising compounds, rodents deficient in mast cells, and inhibition of the actions of mast cell-specific proteases such as chymase and tryptase. Whilst most evidence supports a pro-fibrotic role for mast cells, there is evidence that in some settings these cells can oppose fibrosis. A major gap in our current understanding of cardiac mast cell function is identification of the stimuli that activate these cells causing them to promote a pro-fibrotic environment. This review will present the evidence linking mast cells to cardiac fibrosis, as well as discuss the major questions that remain in understanding how mast cells contribute to cardiac fibrosis.
Highlights
Mast cells (MCs) are non-circulating immune cells that develop only once bone marrow-derived precursors have reached their target tissue
MCs were linked to fibrosis in the hypertensive left ventricle (LV) when Panizo et al [5] observed an increase in MC density in the LV of spontaneously hypertensive rats (SHR) that strongly correlated with collagen volume fraction (r = 0.87)
These results suggest that tryptase acts in an autocrine/paracrine manner to induce chymase release from MCs, and subsequent fibrosis
Summary
Mast cells (MCs) are non-circulating immune cells that develop only once bone marrow-derived precursors have reached their target tissue. These tissue MCs go through several stages of maturation driven primarily by the c-kit ligand, stem cell factor, with the final MC phenotype being highly dependent on the microenvironment in which they reside. Many of the effects of cardiac MCs involve regulation of the extracellular matrix (ECM), whether it be inducing ECM degradation or promoting increased ECM synthesis. The latter characterises cardiac fibrosis, which is a characteristic of almost all cardiac pathologies and is the focus of this review article. This review will discuss important unanswered questions in the field, including the elusive mediators that activate cardiac MCs causing them to promote fibrosis
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