Display options
Cite
Shu Z, Wan J, Read RJ, et al. Angiotensinogen and the Modulation of Blood Pressure. Front Cardiovasc Med. 2021;8:645123doi: 10.3389/fcvm.2021.645123.
Shu, Z., Wan, J., Read, R. J., Carrell, R. W., & Zhou, A. (2021). Angiotensinogen and the Modulation of Blood Pressure. Frontiers in cardiovascular medicine, 8645123. https://doi.org/10.3389/fcvm.2021.645123
Shu, Zimei, et al. "Angiotensinogen and the Modulation of Blood Pressure." Frontiers in cardiovascular medicine vol. 8 (2021): 645123. doi: https://doi.org/10.3389/fcvm.2021.645123
Shu Z, Wan J, Read RJ, Carrell RW, Zhou A. Angiotensinogen and the Modulation of Blood Pressure. Front Cardiovasc Med. 2021 Mar 18;8:645123. doi: 10.3389/fcvm.2021.645123. eCollection 2021. PMID: 33816576; PMCID: PMC8012498.
Copy Download .nbib Format: NLM
Share it on

Front Cardiovasc Med. 2021 Mar 18;8:645123. doi: 10.3389/fcvm.2021.645123. eCollection 2021.

Angiotensinogen and the Modulation of Blood Pressure.

Frontiers in cardiovascular medicine

Zimei Shu, Jiahui Wan, Randy J Read, Robin W Carrell, Aiwu Zhou

Affiliations

  1. Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  2. Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.

PMID: 33816576 PMCID: PMC8012498 DOI: 10.3389/fcvm.2021.645123

Abstract

The angiotensin peptides that control blood pressure are released from the non-inhibitory plasma serpin, angiotensinogen, on cleavage of its extended N-terminal tail by the specific aspartyl-protease, renin. Angiotensinogen had previously been assumed to be a passive substrate, but we describe here how recent studies reveal an inherent conformational mechanism that is critical to the cleavage and release of the angiotensin peptides and consequently to the control of blood pressure. A series of crystallographic structures of angiotensinogen and its derivative forms, together with its complexes with renin show in molecular detail how the interaction with renin triggers a profound shift of the amino-terminal tail of angiotensinogen with modulation occurring at several levels. The tail of angiotensinogen is restrained by a labile disulfide bond, with changes in its redox status affecting angiotensin release, as demonstrably so in the hypertensive complication of pregnancy, pre-eclampsia. The shift of the tail also enhances the binding of renin through a tail-in-mouth allosteric mechanism. The N-terminus is now seen to insert into a pocket equivalent to the hormone-binding site on other serpins, with helix H of angiotensinogen unwinding to form key interactions with renin. The findings explain the precise species specificity of the interaction with renin and with variant carbohydrate linkages. Overall, the studies provide new insights into the physiological regulation of angiotensin release, with an ability to respond to local tissue and temperature changes, and with the opening of strategies for the development of novel agents for the treatment of hypertension.

Copyright © 2021 Shu, Wan, Read, Carrell and Zhou.

Keywords: allosteric; angiotensinogen; hypertension; pre-eclampsia; redox switch; renin; serpin; tail-in-mouth

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. J Soc Gynecol Investig. 2004 Sep;11(6):342-52 - PubMed
  2. Hypertension. 2019 Jun;73(6):1249-1257 - PubMed
  3. Methods Mol Biol. 2020;2073:163-181 - PubMed
  4. Pharmacol Rev. 2007 Sep;59(3):251-87 - PubMed
  5. Am J Hypertens. 2014 May;27(5):656-64 - PubMed
  6. Nature. 1988 Nov 17;336(6196):257-8 - PubMed
  7. N Am J Med Sci (Boston). 2011 Oct 1;4(4):183-190 - PubMed
  8. Biochem J. 1989 Aug 15;262(1):103-7 - PubMed
  9. Med Clin North Am. 2009 May;93(3):621-35 - PubMed
  10. J Biol Chem. 2007 Oct 5;282(40):29594-603 - PubMed
  11. Biochim Biophys Acta. 1987 May 27;913(1):10-9 - PubMed
  12. J Hypertens. 1993 Nov;11(11):1267-74 - PubMed
  13. FEBS Lett. 1998 Oct 2;436(2):267-70 - PubMed
  14. Proc Biol Sci. 2014 Jan 29;281(1779):20132747 - PubMed
  15. J Biol Chem. 2011 May 6;286(18):16163-73 - PubMed
  16. Heart. 1996 Nov;76(3 Suppl 3):7-12 - PubMed
  17. J Biol Chem. 1995 May 12;270(19):11430-6 - PubMed
  18. J Biol Chem. 1998 Dec 18;273(51):34480-7 - PubMed
  19. J Biol Chem. 2019 Feb 15;294(7):2353-2364 - PubMed
  20. Sci Rep. 2020 Feb 6;10(1):1956 - PubMed
  21. Science. 1983 Oct 28;222(4622):417-9 - PubMed
  22. Semin Cell Dev Biol. 2017 Feb;62:133-141 - PubMed
  23. Intensive Crit Care Nurs. 2014 Dec;30(6):325-32 - PubMed
  24. PLoS One. 2014 May 19;9(5):e97879 - PubMed
  25. J Mol Biol. 2008 Jun 27;380(1):244-51 - PubMed
  26. J Clin Invest. 1997 Apr 1;99(7):1786-97 - PubMed
  27. J Clin Endocrinol Metab. 2010 Oct;95(10):4689-95 - PubMed
  28. Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13321-6 - PubMed
  29. Nature. 2010 Nov 4;468(7320):108-11 - PubMed
  30. Methods Mol Biol. 2019;1967:285-293 - PubMed
  31. Nature. 2000 Oct 19;407(6806):923-6 - PubMed
  32. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7806-10 - PubMed
  33. PLoS One. 2015 Aug 27;10(8):e0135905 - PubMed
  34. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2735-9 - PubMed

Publication Types

Grant support