Role of mast cells and their chymases in the development of cardiac hypertrophy

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Cardiac hypertrophy or heart enlargement is an important risk factor in the eventual development of heart failure. It is now well known that heart enlargement can be produced by pressure overload of hypertension and-or by increased hormonal inputs directly to the heart. Angiotensin ll, a hormone that produces hypertension and heart enlargement, was previously thought only to be produced by the enzyme ACE. Although ACE inhibitors are widely used in treatment of hypertension and heart failure several studies now show that ACE inhibition only partially reduces angiotensin ll levels in humans. Our ecent studies suggest that the novel enzyme human chymase may be involved in regulating angiotensin ll levels in human tissues including the heart and blood vessels. The proposed studies seek to establish the role of chymase, and the cell type (mast cell) that elaborates it, in the development of cardiac hypertrophy.