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Angiotensin-converting enzyme 2: enhancing the degradation of angiotensin II as a potential therapy for diabetic nephropathy

Journal

KIDNEY INTERNATIONAL
Volume 81, Issue 6, Pages 520-528

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ki.2011.381

Keywords

angiotensin; diabetic nephropathy; renin-angiotensin system

Funding

  1. National Institute of Diabetes and Digestive Kidney Diseases [1R01DK080089-01A2]
  2. Juvenile Diabetes Research Foundation
  3. Fondo de Investigacion Sanitaria Instituto Carlos III, Spain
  4. Fundacion Senefro

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Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin II with high efficiency leading to the formation of angiotensin-(1-7). ACE2 within the kidneys is largely localized in tubular epithelial cells and in glomerular epithelial cells. Decreased glomerular expression of this enzyme coupled with increased expression of ACE has been described in diabetic kidney disease, both in mice and humans with type 2 diabetes. Moreover, both ACE2 genetic ablation and pharmacological ACE2 inhibition have been shown to increase albuminuria and promote glomerular injury. Studies using recombinant ACE2 have shown the ability of ACE2 to rapidly metabolize Ang II in vivo and form the basis for future studies to examine the potential of ACE2 amplification in the therapy of diabetic kidney disease and cardiovascular disease. Kidney International (2012) 81, 520-528; doi: 10.1038/ki.2011.381; published online 23 November 2011

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