ACE2, a New Regulator of the Renin Angiotensin System

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Angiotensin converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS), converting Angiotensin I to the potent vasoconstrictor Angiotensin II (Ang II). ACE inhibitors have been highly successful in the management of hypertension, are standard therapy following myocardial infarction to delay the development of heart failure, and also reduce the rate of progression of renal disease. Recently, a novel enzyme called ACE2 has been discovered in the heart and kidneys. Unlike ACE, ACE2 causes the formation of the vasodilator, Ang 1-7. We have data in the heart and the kidney that supports the concept that ACE2 acts in a counter-regulatory manner to ACE. We suggest that ACE2 may play an important role to modulate the balance between vasoconstrictors and vasodilators in the heart and kidney. The studies detailed in this proposal are designed to specifically examine the role and regulation of ACE2 in the healthy heart and kidney as well as in cardiovascular and renal disease. The project brings together two groups with complementary skills and techniques, both of whom have collaborations with the discoverers of ACE2, and who have been exploring the role of ACE2 as evidenced from our recent publication (Tikellis et al, Hypertension in press, 2003).