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The emerging role of angiotensin-converting enzyme-2 in the kidney.

Burns KD

Kidney Research Centre, Division of Nephrology, The Ottawa Hospital, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada. kburns@ottawahospital.on.ca

PURPOSE OF REVIEW: The intrarenal renin-angiotensin system contributes to the progression of chronic kidney disease. Angiotensin-converting enzyme-2 is a recently identified protein that is highly expressed in the kidney and results in formation of angiotensin-(1-7). This manuscript highlights current information on the localization and function of angiotensin-converting enzyme-2 in the kidney, along with recent studies on the role of the enzyme in hypertension, glomerulosclerosis, and diabetic nephropathy. RECENT FINDINGS: Angiotensin-converting enzyme-2 is expressed in relative abundance in the proximal tubule and metabolizes angiotensin II to angiotensin-(1-7). Angiotensin-converting enzyme-2 also catalyzes conversion of angiotensin I to angiotensin-(1-9), which is cleaved to angiotensin-(1-7) by angiotensin-converting enzyme. In mice, gene deletion of angiotensin-converting enzyme-2 elevates blood pressure responses to angiotensin II, and increases renal angiotensin II levels. Male angiotensin-converting enzyme-2-deficient mice exhibit accelerated glomerulosclerosis. In early diabetic nephropathy, proximal tubular angiotensin-converting enzyme-2 expression and activity are increased, suggesting that the enzyme may counterregulate the effects of local angiotensin II. SUMMARY: Angiotensin-converting enzyme-2 appears to be critical in determining the balance between the intrarenal effects of angiotensin II and angiotensin-(1-7). Angiotensin-converting enzyme-2 could thereby represent a target for novel therapeutic approaches in a variety of kidney disorders.

Published 12 February 2007 in Curr Opin Nephrol Hypertens, 16(2): 116-21.
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