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


RESULTS
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.


CONCLUSIONS
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.
Burns
Kevin D
KD
Kidney Research Centre, Division of Nephrology, The Ottawa Hospital, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada. kburns@ottawahospital.on.ca
D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2