Cardiac Mast Cells as Mediators of Ventricular Remodeling

Summary

Mast cells are known to store and release a variety of biologically active mediators including TNF-α, and proteases such as tryptase and chymase. With cardiac chamber distension there is a release of atrial natriuretic peptide, which is known to cause mast cell degranulation (Figure 2). Secreted TNF-α tryptase and chymase are all capable of activating matrix metalloproteinases, which in turn are responsible for fibrillar collagen degradation. Since one of the roles of the extracellular collagen matrix is to maintain ventricular size and shape, its disruption results in adverse remodeling. Also secreted from the mast cell is a yet to be identified substance that stimulates the maturation of resident immature mast cells. Proof of mast cell involvement in these processes is provided by the use of mast cell membrane stabilizing compounds such as cromolyn sodium, which prevent mast cell degranulation. These drugs prevent the activation of MMPs, degradation of collagen, the increase in mast cell density, adverse ventricular remodeling, and the decrease in contractility as well as attenuate the morbidity/mortality associated with chronic volume overload. They are similarly efficacious in preventing the onset of heart failure in hearts subjected to chronic pressure overload. Finally, evidence is rapidly emerging which identifies mast cell-derived TNF-α and/or the downstream cytokine cascade it induces as a major contributor to adverse ventricular remodeling and associated contractile dysfunction.