Role Of Mast Cells And Their Chymases In The Development Of Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$378,000.00
Summary
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 seve ....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.Read moreRead less
A Transgenic Mouse Model For Studying The Role Of Human Chymase In Regulating Tissue Angiotensin II Formation
Funder
National Health and Medical Research Council
Funding Amount
$536,063.00
Summary
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 II, 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 seve ....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 II, 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 II levels in humans. Our recent studies suggest that the novel enzyme human chymase may be involved in regulating angiotensin II levels in human tissues including the heart and blood vessels. By introducing a gene for human chymase in mice we plan to create a mouse model that allows us to understand the importance of human chymase in cardiovascular physiology and disease. This mouse model would not only show the involvement of human chymase in regulating heart and vessel angiotensin II levels and in the development of hypertension and heart enlargement but also will provide an animal model essential for the development of human chymase inhibitors.Read moreRead less