ACE2 alterations in kidney disease.
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Journal: 2014/October - Nephrology Dialysis Transplantation
ISSN: 1460-2385
Abstract:
Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1-7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance.
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Nephrol Dial Transplant 28(11): 2687-2697
PMID: 23956234

ACE2 alterations in kidney disease

ACKNOWLEDGEMENTS

D.B. received grant support from NIDDK (1 R01 DK080089). M.S. received grant support from the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (ISCIII-FEDER. PI11/01549). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health.

REFERENCES

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Department of Nephrology, Hospital del Mar-Fundació IMIM, Barcelona, Spain
Division of Nephrology & Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Correspondence and offprint requests to: María José Soler; E-mail: tac.ramtulasedcrap@relosM
Received 2013 Jun 13; Accepted 2013 Jun 20.
Copyright © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1–7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance.

Keywords: ACE2, kidney disease, renin–angiotensin system
Abstract

*In glomeruli, ACE2 expression by immunostaining has been found to be decreased [24–26].

REFERENCES

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3. Tipnis SR, Hooper NM, Hyde R, et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275:33238–33243. [PubMed] [Google Scholar]
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5. Hamming I, Timens W, Bulthuis ML, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–637. [PubMed] [Google Scholar]
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11. Ye M, Wysocki J, Naaz P, et al. Increased ACE 2 and decreased ACE protein in renal tubules from diabetic mice: a renoprotective combination? Hypertension. 2004;43:1120–1125. [PubMed] [Google Scholar]
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14. Oudit GY, Liu GC, Zhong J, et al. Human recombinant ACE2 reduces the progression of diabetic nephropathy. Diabetes. 2010;59:529–538.[PMC free article] [PubMed] [Google Scholar]
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16. Wysocki J, Soler M, Ye M, et al. ACE2 is critically important for angiotensin II metabolism in podocytes. J. Am. Soc. Nephrol. 2006;17:TH-PO877.293A.[Google Scholar]
17. Tikellis C, Bialkowski K, Pete J, et al. ACE2 deficiency modifies renoprotection afforded by ACE inhibition in experimental diabetes. Diabetes. 2008;57:1018–1025. [PubMed] [Google Scholar]
18. Prieto MC, Gonzalez-Villalobos RA, Botros FT, et al. Reciprocal changes in renal ACE/ANG II and ACE2/ANG 1–7 are associated with enhanced collecting duct renin in Goldblatt hypertensive rats. Am J Physiol. Renal Physiol. 2011;300:F749–55. [Research Support, N.I.H., Extramural Research Support, Non-US Gov't] [PMC free article] [PubMed] [Google Scholar]
19. Samuel P, Ali Q, Sabuhi R, et al. High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT(2)R-MasR axis in obese Zucker rats. Am J Physiol Renal Physiol. 2012;303:F412–F419. [Research Support, N.I.H., Extramural Research Support, Non-US Govt] [PMC free article] [PubMed] [Google Scholar]
20. Mizuiri S, Hemmi H, Arita M, et al. Increased ACE and decreased ACE2 expression in kidneys from patients with IgA nephropathy. Nephron Clin Pract. 2011;117:c57–c66. [Research Support, Non-US Govt] [PubMed] [Google Scholar]
21. Velkoska E, Dean RG, Burchill L, et al. Reduction in renal ACE2 expression in subtotal nephrectomy in rats is ameliorated with ACE inhibition. Clin Sci. 2010;118:269–279. [Research Support, Non-US Govt] [PMC free article] [PubMed] [Google Scholar]
22. da Silveira KD, Pompermayer Bosco KS, Diniz LR, et al. ACE2-angiotensin-(1–7)-Mas Axis in renal ischaemia/reperfusion injury in rats. Clin Sci. 2010;119:385–394. [Research Support, Non-US Govt] [PubMed] [Google Scholar]
23. Gupta A, Rhodes GJ, Berg DT, et al. Activated protein C ameliorates LPS-induced acute kidney injury and downregulates renal INOS and angiotensin 2. Am J Physiol Renal Physiol. 2007;293:F245–F254. [PubMed] [Google Scholar]
24. Mizuiri S, Hemmi H, Arita M, et al. Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls. Am J Kidney Dis. 2008;51:613–623. [PubMed] [Google Scholar]
25. Batlle D, Soler MJ, Wysocki J. New aspects of the renin-angiotensin system: angiotensin-converting enzyme 2—a potential target for treatment of hypertension and diabetic nephropathy. Curr Opin Nephrol Hypertens. 2008;17:250–257. [PubMed] [Google Scholar]
26. Tikellis C, Johnston CI, Forbes JM, et al. Characterization of renal angiotensin-converting enzyme 2 in diabetic nephropathy. Hypertension. 2003;41:392–397. [PubMed] [Google Scholar]
27. Batlle D, Wysocki J, Soler MJ, et al. Angiotensin-converting enzyme 2: enhancing the degradation of angiotensin II as a potential therapy for diabetic nephropathy. Kidney Int. 2012;81:520–528. [PubMed] [Google Scholar]
28. Moon JY, Jeong KH, Lee SH, et al. Renal ACE and ACE2 expression in early diabetic rats. Nephron Exp Nephrol. 2008;110:e8–e16. [PubMed] [Google Scholar]
29. Leehey DJ, Singh AK, Bast JP, et al. Glomerular renin angiotensin system in streptozotocin diabetic and Zucker diabetic fatty rats. Transl Res. 2008;151:208–216. [PubMed] [Google Scholar]
30. Chodavarapu H, Grobe N, Somineni HK, et al. Rosiglitazone treatment of type 2 diabetic db/db mice attenuates urinary albumin and angiotensin converting enzyme 2 excretion. PLoS ONE. 2013;8:e62833.[PMC free article] [PubMed] [Google Scholar]
31. Reich HN, Oudit GY, Penninger JM, et al. Decreased glomerular and tubular expression of ACE2 in patients with type 2 diabetes and kidney disease. Kidney Int. 2008;74:1610–1616. [PubMed] [Google Scholar]
32. Nadarajah R, Milagres R, Dilauro M, et al. Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice. Kidney Int. 2012;82:292–303. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Govt] [PMC free article] [PubMed] [Google Scholar]
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  • 58. Wakahara S, Konoshita T, Mizuno S, et al Synergistic expression of angiotensin-converting enzyme (ACE) and ACE2 in human renal tissue and confounding effects of hypertension on the ACE to ACE2 Ratio. Endocrinology. 2007;148:2453–2457.[PubMed][Google Scholar]
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