Skip to main content

Advertisement

SpringerLink
Log in
Menu
Find a journal Publish with us
Search
Cart
  1. Home
  2. Current Hypertension Reports
  3. Article
Pharmacologic modulation of ACE2 expression
Download PDF
Download PDF
  • Published: 16 October 2008

Pharmacologic modulation of ACE2 expression

  • María José Soler,
  • Clara Barrios,
  • Raymond Oliva &
  • …
  • Daniel Batlle1 

Current Hypertension Reports volume 10, pages 410–414 (2008)Cite this article

  • 1792 Accesses

  • 59 Citations

  • 22 Altmetric

  • Metrics details

Abstract

Angiotensin-converting enzyme 2 (ACE2) is an enzymatically active homologue of angiotensin-converting enzyme that degrades angiotensin I, angiotensin II, and other peptides. Recent studies have shown that under pathologic conditions, ACE2 expression in the kidney is altered. In this review, we briefly summarize recent studies dealing with pharmacologic interventions that modulate ACE2 expression. ACE2 amplification may have a potential therapeutic role for kidney disease and hypertension.

Download to read the full article text

Working on a manuscript?

Avoid the common mistakes

References and Recommended Reading

  1. Danilczyk U, Penninger JM: Angiotensin-converting enzyme II in the heart and the kidney. Circ Res 2006, 98:463–471.

    Article  PubMed  CAS  Google Scholar 

  2. 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, 275:332 38–332 43.

    Article  CAS  Google Scholar 

  3. Donoghue M, Hsieh F, Baronas E, et al.: A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res 2000, 87:E1–E9.

    PubMed  CAS  Google Scholar 

  4. Crackower MA, Sarao R, Oudit GY, et al.: Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 2002, 417:822–828.

    Article  PubMed  CAS  Google Scholar 

  5. Xie X, Chen J, Wang X, et al.: Age-and gender-related difference of ACE2 expression in rat lung. Life Sci 2006, 78:2166–2171.

    Article  PubMed  CAS  Google Scholar 

  6. Valdes G, Neves LA, Anton L, et al.: Distribution of angiotensin-(1–7) and ACE2 in human placentas of normal and pathological pregnancies. Placenta 2006, 27:200–207.

    Article  PubMed  CAS  Google Scholar 

  7. Paizis G, Tikellis C, Cooper ME, et al.: Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut 2005, 54:1790–1796.

    Article  PubMed  CAS  Google Scholar 

  8. Imai Y, Kuba K, Rao S, et al.: Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005, 436:112–116.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. Doobay MF, Talman LS, Obr TD, et al.: Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol 2007, 292:R373–R381.

    PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Soler MJ, Wysocki J, Batlle D: ACE2 and the kidney. Exp Physiol 2008, 93:549–553.

    Article  PubMed  CAS  Google Scholar 

  13. Soler MJ, Wysocki J, Ye M, et al.: ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice. Kidney Int 2007, 72:614–623.

    Article  PubMed  CAS  Google Scholar 

  14. Tikellis C, Cooper ME, Bialkowski K, et al.: Developmental expression of ACE2 in the SHR kidney: a role in hypertension? Kidney Int 2006, 70:34–41.

    Article  PubMed  CAS  Google Scholar 

  15. Wysocki J, Ye M, Soler MJ, et al.: ACE and ACE2 activity in diabetic mice. Diabetes 2006, 55:2132–2139.

    Article  PubMed  CAS  Google Scholar 

  16. Ye M, Wysocki J, William J, et al.: Glomerular localization and expression of Angiotensin-converting enzyme 2 and Angiotensin-converting enzyme: implications for albuminuria in diabetes. J Am Soc Nephrol 2006, 17:3067–3075.

    Article  PubMed  CAS  Google Scholar 

  17. Zhong JC, Huang DY, Yang YM, et al.: Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in spontaneously hypertensive rats. Hypertension 2004, 44:907–912.

    Article  PubMed  CAS  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. Wysocki J, Gonzalez-Pacheco FR, Batlle D: Angiotensin-converting enzyme 2: possible role in hypertension and kidney disease. Curr Hypertens Rep 2008, 10:70–77.

    Article  PubMed  CAS  Google Scholar 

  21. Wong DW, Oudit GY, Reich H, et al.: Loss of angiotensin-converting enzyme-2 (Ace2) accelerates diabetic kidney injury. Am J Pathol 2007, 171:438–451.

    Article  PubMed  CAS  Google Scholar 

  22. Brosnihan KB, Neves LA, Joyner J, et al.: Enhanced renal immunocytochemical expression of ANG-(1–7) and ACE2 during pregnancy. Hypertension 2003, 42:749–753.

    Article  PubMed  CAS  Google Scholar 

  23. de Lang A, Osterhaus AD, Haagmans BL: Interferon-gamma and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells. Virology 2006, 353:474–481.

    Article  PubMed  CAS  Google Scholar 

  24. Keidar S, Gamliel-Lazarovich A, Kaplan M, et al.: Mineralocorticoid receptor blocker increases angiotensin-converting enzyme 2 activity in congestive heart failure patients. Circ Res 2005, 97:946–953.

    Article  PubMed  CAS  Google Scholar 

  25. Gallagher PE, Chappell MC, Ferrario CM, Tallant EA: Distinct roles for ANG II and ANG-(1–7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes. Am J Physiol Cell Physiol 2006, 290:C420–C426.

    Article  PubMed  CAS  Google Scholar 

  26. Koka V, Huang XR, Chung AC, et al.: Angiotensin II up-regulates angiotensin I-converting enzyme (ACE), but down-regulates ACE2 via the AT1-ERK/p38 MAP kinase pathway. Am J Pathol 2008, 172:1174–1183.

    Article  PubMed  CAS  Google Scholar 

  27. Zulli A, Rai S, Buxton BF, et al.: Co-localization of angiotensin-converting enzyme 2-, octomer-4-and CD34-positive cells in rabbit atherosclerotic plaques. Exp Physiol 2008, 93:564–569.

    Article  PubMed  Google Scholar 

  28. Ji H, Menini S, Zheng W, et al.: Role of angiotensin-converting enzyme 2 and angiotensin(1–7) in 17beta-oestradiol regulation of renal pathology in renal wrap hypertension. Exp Physiol 2008, 93:648–657.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. Soler MJ, Wysocki J, William J, et al.: ACE2 is preferentially localized in the tunica media layer in renal vasculature and its expression increases after administration of a type 1 receptor antagonist [abstract]. Hypertension 2006, 48:E25–E103 LB 12.

    Article  CAS  Google Scholar 

  31. Ocaranza MP, Godoy I, Jalil JE, et al.: Enalapril attenuates downregulation of angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat. Hypertension 2006, 48:572–578.

    Article  PubMed  CAS  Google Scholar 

  32. Igase M, Strawn WB, Gallagher PE, et al.: Angiotensin II AT1 receptors regulate ACE2 and angiotensin-(1–7) expression in the aorta of spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 2005, 289:H1013–H1019.

    Article  PubMed  CAS  Google Scholar 

  33. Ferrario CM, Jessup J, Gallagher PE, et al.: Effects of renin-angiotensin system blockade on renal angiotensin-(1–7) forming enzymes and receptors. Kidney Int 2005, 68:2189–2196.

    Article  PubMed  CAS  Google Scholar 

  34. Takeda Y, Zhu A, Yoneda T, et al.: Effects of aldosterone and angiotensin II receptor blockade on cardiac angiotensinogen and angiotensin-converting enzyme 2 expression in Dahl salt-sensitive hypertensive rats. Am J Hypertens 2007, 20:1119–1124.

    Article  PubMed  CAS  Google Scholar 

  35. Jessup JA, Gallagher PE, Averill DB, et al.: 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.

    Article  PubMed  CAS  Google Scholar 

  36. Agata J, Ura N, Yoshida H, et al.: Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. Hypertens Res 2006, 29:865–874.

    Article  PubMed  CAS  Google Scholar 

  37. Whaley-Connell AT, Chowdhury NA, Hayden MR, et al.: Oxidative stress and glomerular filtration barrier injury: role of the renin-angiotensin system in the Ren2 transgenic rat. Am J Physiol Renal Physiol 2006, 291:F1308–F1314.

    Article  PubMed  CAS  Google Scholar 

  38. Yamamoto K, Ohishi M, Katsuya T, et al.: Deletion of angiotensin-converting enzyme 2 accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensin II. Hypertension 2006, 47:718–726.

    Article  PubMed  CAS  Google Scholar 

  39. Oudit GY, Kassiri Z, Patel MP, et al.: Angiotensin II-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice. Cardiovasc Res 2007, 75:29–39.

    Article  PubMed  CAS  Google Scholar 

  40. Benson SC, Pershadsingh HA, Ho CI, et al.: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension 2004, 43:993–1002.

    Article  PubMed  CAS  Google Scholar 

  41. Yamagishi S, Takeuchi M: Telmisartan is a promising cardiometabolic sartan due to its unique PPAR-gamma-inducing property. Med Hypotheses 2005, 64:476–478.

    Article  PubMed  CAS  Google Scholar 

  42. Kobayashi N, Ohno T, Yoshida K, et al.: Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. Am J Hypertens 2008, 21:576–581.

    Article  PubMed  CAS  Google Scholar 

  43. Tikellis C, Bialkowski K, Pete J, et al.: ACE2 deficiency modifies renoprotection afforded by ACE inhibition in experimental diabetes. Diabetes 2008, 57:1018–1025.

    Article  PubMed  CAS  Google Scholar 

  44. Hernandez Prada JA, Ferreira AJ, Katovich MJ, et al.: Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents. Hypertension 2008, 51:1312–1317.

    Article  PubMed  CAS  Google Scholar 

  45. Ye M, Wysocki J, Rodriguez E, et al.: Recombinant ACE2 attenuates angiotensin II induced hypertension [abstract]. Hypertension 2007, 50:e75–e155.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, 320 East Superior, Chicago, IL, 60611, USA

    Daniel Batlle

Authors
  1. María José Soler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clara Barrios
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raymond Oliva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel Batlle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel Batlle.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Soler, M.J., Barrios, C., Oliva, R. et al. Pharmacologic modulation of ACE2 expression. Current Science Inc 10, 410–414 (2008). https://doi.org/10.1007/s11906-008-0076-0

Download citation

  • Published: 16 October 2008

  • Issue Date: October 2008

  • DOI: https://doi.org/10.1007/s11906-008-0076-0

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Telmisartan
  • Olmesartan
  • Eplerenone
  • ACE2 Activity
  • ACE2 Protein
Download PDF

Working on a manuscript?

Avoid the common mistakes

Advertisement

Search

Navigation

  • Find a journal
  • Publish with us

Discover content

  • Journals A-Z
  • Books A-Z

Publish with us

  • Publish your research
  • Open access publishing

Products and services

  • Our products
  • Librarians
  • Societies
  • Partners and advertisers

Our imprints

  • Springer
  • Nature Portfolio
  • BMC
  • Palgrave Macmillan
  • Apress
  • Your US state privacy rights
  • Accessibility statement
  • Terms and conditions
  • Privacy policy
  • Help and support

65.108.231.39

Not affiliated

Springer Nature

© 2023 Springer Nature