New aspects of the renin-angiotensin system: angiotensin-converting enzyme 2 - a potential target for treatment of hypertension and diabetic nephropathy.
OBJECTIVE
Whereas angiotensin-converting enzyme promotes the formation of angiotensin II, angiotensin-converting enzyme 2 promotes the degradation of angiotensin II to angiotensin-(1-7). We review recent studies dealing with angiotensin-converting enzyme 2 in kidney disease and hypertension, and discuss the potential therapeutic benefit of increasing angiotensin-converting enzyme 2 activity in the treatment of these diseases.


RESULTS
In glomeruli from diabetic mice, angiotensin-converting enzyme 2 expression is downregulated, and pharmacological inhibition of angiotensin-converting enzyme 2 leads to worsening of albuminuria, increased mesangial matrix deposition and fibronectin expression. The deletion of the angiotensin-converting enzyme 2 gene in mice leads to worsening of angiotensin II-induced hypertension and has also been shown to cause glomerulosclerosis in aging male mice.


CONCLUSIONS
Angiotensin-converting enzyme 2 is a key enzyme in the renin-angiotensin system that favors the degradation of angiotensin I and angiotensin II. Angiotensin-converting enzyme 2 inhibition by pharmacological means and by genetic deletion worsens kidney disease in diabetic mice. Strategies geared to increasing angiotensin-converting enzyme 2 activity may provide a novel therapeutic target within the renin-angiotensin system by enhancing angiotensin II degradation that may complement the current approach of inhibiting angiotensin II formation and action. Amplifying angiotensin-converting enzyme 2 activity may have a potential therapeutic role for kidney disease and hypertension.
Batlle
Daniel
D
Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. d-batlle@northwestern.edu
Soler
María José
MJ
Wysocki
Jan
J
D000085962:Angiotensin-Converting Enzyme 2; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000627:therapeutic use*; D015316:Genetic Therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics
D000809:Angiotensins; D000959:Antihypertensive Agents; D020536:Enzyme Activators; D011994:Recombinant Proteins; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2