Kidney and Blood Pressure Research

Original Paper

Free Access

Expression of ACE and ACE2 in Patients with Hypertensive Nephrosclerosis

Wang G.a, c · Lai F.M.-M.b · Kwan B.C.H.a · Lai K.-B.a · Chow K.-M.a · Li P.K.T.a · Szeto C.-C.a

Author affiliations

Departments of aMedicine and Therapeutics and bAnatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR and cDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China

Corresponding Author

Dr. C.C. Szeto

Department of Medicine and Therapeutics

Prince of Wales Hospital, The Chinese University of Hong Kong

Shatin, NT, Hong Kong, SAR (China)

Tel. +852 2632 3126, E-Mail ccszeto@cuhk.edu.hk

Keywords: HypertensionACE2Renal disease

Related Articles for ""
Kidney Blood Press Res 2011;34:141–149
https://doi.org/10.1159/000324521

Abstract

Background: The interplay between intrarenal angiotensin-converting enzyme (ACE) and type 2 ACE (ACE2) might play important roles in the pathogenesis of hypertensive nephrosclerosis (HTN), but human data are limited. Methods: Renal biopsy specimens of 41 patients with HTN and 10 transplant donors as controls (CTL) were studied. The glomerular and tubulointerstitial mRNA expression of ACE and ACE2 was measured by laser microdissection and real-time quantitative polymerase chain reaction. The corresponding protein level was determined by immunohistochemistry. Results: Neither the glomerular nor tubulointerstitial mRNA expression of ACE or ACE2 correlated with the corresponding protein level by immunohistochemistry. The tubulointerstitial levels of ACE and ACE2 were significantly lower in HTN than CTL, while the glomerular ACE and ACE2 levels were similar between the groups. The tubulointersitial ACE and ACE2 levels significantly correlated with the estimated glomerular filtration rate (GFR) and inversely with the degree of histological damage. The glomerular ACE and ACE2 levels significantly correlated with the rate of GFR decline. The ratio of glomerular ACE and ACE2 level correlated with the estimated GFR and the degree of glomerulosclerosis. Conclusion: Our results suggest that intrarenal ACE and ACE2 may play an important role in the pathogenesis and progression of HTN. Studies based on the mRNA expression of ACE and ACE2 should be cautiously interpreted.

© 2011 S. Karger AG, Basel



Related Articles:

References

  1. USRDS: 2007 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2007.
  2. ERA-EDTA: Registry 2005 Annual Report. Amsterdam, Academic Medical Centre, 2007.
  3. Opie LH: Renoprotection by angiotensin-receptor blockers and ACE inhibitors in hypertension. Lancet 2001;358:1829–1831.
    External Resources
  4. Navar LG: The intrarenal renin-angiotensin system in hypertension. Kidney Int 2004;65:1522–1532.
    External Resources
  5. Kobori H, Nangaku M, Navar LG, Nishiyama A: The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 2007;59:251–287.
    External Resources
  6. Bidani AK, Griffin KA: Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension 2004;44:595–601.
    External Resources
  7. Fakhouri F, Placier S, Ardaillou R, Dussaule JC, Chatziantoniou C: Angiotensin II activates collagen type I gene in the renal cortex and aorta of transgenic mice through interaction with endothelin and TGF-β. J Am Soc Nephrol 2001;12:2701–2710.
    External Resources
  8. Dussaule JC, Tharaux PL, Boffa JJ, Fakhouri F, Ardaillou R, Chatziantoniou C: Mechanisms mediating the renal profibrotic actions of vasoactive peptides in transgenic mice. J Am Soc Nephrol 2000;11(suppl 16):S124–S128.
    External Resources
  9. Lai KN, Leung JC, Lai KB, To WY, Yeung VT, Lai FM: Gene expression of the renin-angiotensin system in human kidney. J Hypertens 1998;16:91–102.
    External Resources
  10. Burrell LM, Johnston CI, Tikellis C, Cooper ME: ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab 2004;15:166–169.
    External Resources
  11. Thomas MC, Tikellis C: ACE2: an ACE up the sleeve? Curr Enzym Inhib 2005;1:51–63.
    External Resources
  12. Fogo A, Weedman B, Solez K: Hypertensive nephrosclerosis; in Atlas of Renal Pathology. Nashville, The National Kidney Foundation, 1999.
  13. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461–470.
    External Resources
  14. Chan RW, Lai FM, Li EK, Tam LS, Chow KM, Lai KB, Li PK, Szeto CC: Intrarenal cytokine gene expression in lupus nephritis. Ann Rheum Dis 2007;66:886–892.
    External Resources
  15. Applied Biosystems: Guide to Performing Relative Quantitation of Gene Expression Using Real-Time Quantitative PCR. Foster City, Applied Biosystems, 2004.
  16. Wang G, Lai FM, Lai KB, Chow KM, Li KT, Szeto CC: Messenger RNA expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy. Nephron Clin Pract 2007;106: c169–c179.
    External Resources
  17. Szeto CC, Chow KM, Lai KB, Szeto CY, Chan RW, Kwan BC, Chung KY, Li PK, Lai FM: mRNA expression of target genes in the urinary sediment as a noninvasive prognostic indicator of CKD. Am J Kidney Dis 2006;47:578–586.
    External Resources
  18. Mitch W: Measuring the rate of progression of renal insufficiency; in Mitch WE, Stein J, Brenner BM (eds): The Progressive Nature of Renal Disease. New York, Churchill Livingstone, 1986, pp 203–220.
  19. Ichihara A, Hayashi M, Kaneshiro Y, Suzuki F, Nakagawa T, Tada Y, Koura Y, Nishiyama A, Okada H, Uddin MN, et al: Inhibition of diabetic nephropathy by a decoy peptide corresponding to the ‘handle’ region for nonproteolytic activation of prorenin. J Clin Invest 2004;114:1128–1135.
    External Resources
  20. Tikellis C, Johnston CI, Forbes JM, Burns WC, Burrell LM, Risvanis J, Cooper ME: Characterization of renal angiotensin-converting enzyme 2 in diabetic nephropathy. Hypertension 2003;41:392–397.
    External Resources
  21. Wysocki J, Ye M, Soler MJ, Gurley SB, Xiao HD, Bernstein KE, Coffman TM, Chen S, Batlle D: ACE and ACE2 activity in diabetic mice. Diabetes 2006;55:2132–2139.
    External Resources
  22. Ye M, Wysocki J, Naaz P, Salabat MR, LaPointe MS, Batlle D: Increased ACE2 and decreased ACE protein in renal tubules from diabetic mice: a renoprotective combination? Hypertension 2004;43:1120–1125.
    External Resources
  23. Zhong JC, Huang DY, Yang YM, Li YF, Liu GF, Song XH, Du K: Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in spontaneously hypertensive rats. Hypertension 2004;44:907–912.
    External Resources
  24. Konoshita T, Wakahara S, Mizuno S, Motomura M, Aoyama C, Makino Y, Kawai Y, Kato N, Koni I, Miyamori I, et al: Tissue gene expression of renin-angiotensin system in human type 2 diabetic nephropathy. Diabetes Care 2006;29:848–852.
    External Resources
  25. Mizuiri S, Hemmi H, Arita M, Ohashi Y, Tanaka Y, Miyagi M, Sakai K, Ishikawa Y, Shibuya K, Hase H, et al: Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls. Am J Kidney Dis 2008;51:613–623.
    External Resources
  26. Ingelfinger JR: ACE2: a new target for prevention of diabetic nephropathy? J Am Soc Nephrol 2006;17:2957–2959.
    External Resources
  27. Lely AT, Hamming I, van Goor H, Navis GJ: Renal ACE2 expression in human kidney disease. J Pathol 2004;204:587–593.
    External Resources
  28. Mezzano S, Droguett A, Burgos ME, Ardiles LG, Flores CA, Aros CA, Caorsi I, Vio CP, Ruiz-Ortega M, Egido J: Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney Int 2003;64(suppl 86):S64–S70.
    External Resources
  29. Wakahara S, Konoshita T, Mizuno S, Motomura M, Aoyama C, Makino Y, Kato N, Koni I, Miyamori I: 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.
    External Resources
  30. Bomback AS, Klemmer PJ: The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol 2007;3:486–492.
    External Resources
  31. Jessup JA, Gallagher PE, Averill DB, Brosnihan KB, Tallant EA, Chappell MC, Ferrario CM: Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats. Am J Physiol Heart Circ Physiol 2006;291:H2166–H2172.
    External Resources
  32. Santa Cruz Biotechnology, Inc. ACE (H-170): sc-20791. Website: http://datasheets.scbt.com/sc-20791.pdf (last accessed on January 10, 2011).
  33. Abcam: Angiotensin-converting enzyme 2 antibody (ab15348). Website: http://www. abcam.com/Angiotensin-Converting- Enzyme-2-antibody-ab15348.html (last accessed on January 10, 2011).
  34. Hemming ML, Selkoe DJ: Amyloid β-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. J Biol Chem 2005;280:37644–37650.
    External Resources
  35. Wang G, Lai FM, Lai KB, Chow KM, Kwan CH, Li KT, Szeto CC: Discrepancy between intrarenal messenger RNA and protein expression of ACE and ACE2 in human diabetic nephropathy. Am J Nephrol 2009;29:524–531.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: August 26, 2010
Accepted: January 17, 2011
Published online: February 24, 2011
Issue release date: May 2011

Number of Print Pages: 9
Number of Figures: 7
Number of Tables: 1

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)

For additional information: https://www.karger.com/KBR

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Article Tools
Article Details

2011, Vol.34, No. 3

May 2011

Article

Recommend This
Open Access Gateway
TOP