Kevin D Burns1. 1. Kidney Research Centre, Division of Nephrology, The Ottawa Hospital, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada. kburns@ottawahospital.on.ca
Abstract
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.
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.
Authors: Juan Carlos Q Velez; Jessalyn L Ierardi; Alison M Bland; Thomas A Morinelli; John M Arthur; John R Raymond; Michael G Janech Journal: Am J Physiol Renal Physiol Date: 2012-03-28
Authors: Jan Wysocki; Minghao Ye; Eva Rodriguez; Francisco R González-Pacheco; Clara Barrios; Karla Evora; Manfred Schuster; Hans Loibner; K Bridget Brosnihan; Carlos M Ferrario; Josef M Penninger; Daniel Batlle Journal: Hypertension Date: 2009-11-30 Impact factor: 10.190
Authors: Kathryn M Gauthier; David X Zhang; Lijie Cui; Kasem Nithipatikom; William B Campbell Journal: Hypertension Date: 2008-05-19 Impact factor: 10.190