Skip to main content
SpringerLink
Log in

Angiotensin II Regulated Apoptosis in Cardiovascular Remodeling

  • Chapter
Angiotensin II Receptor Blockade Physiological and Clinical Implications

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 2))

  • 108 Accesses

Summary

Angiotensin (Ang) II exerts major influences on the heart and blood vessels via its effects on systemic hemodynamics and blood volume as well as structural effects. The major cardiovascular actions of Ang II have been reported to be mediated by the type 1 Ang II receptor or AT1 receptor. Recently, we have cloned a second receptor subtype known as AT2 receptor. The existence and differential expression of two different subtypes of Ang II receptors in the human myocardium and the reciprocal expression of AT1 and AT2 receptor in myocardial infarction and cardiac failure suggest pathophysiological importance of these receptors in cardiovascular disease and remodeling. Moreover, documented evidences suggest that the cellular composition of the heart and blood vessels is determined by the balance between apoptotic cell death (programmed cell death) and cell survival, and the unbalanced cell death plays a critical role in the pathogenesis of cardiovascular diseases and remodeling. Our successful clonings of AT2 receptor cDNAs have provided a unique opportunity to study the biology and function of this receptor. Indeed, in our previous experiments, we have demonstrated that AT2 receptor activates tyrosine phosphatase(s) and inhibits mitogen-activated protein kinase (MAPK) activation, thereby exerting the proapoptotic and antigrowth effects in several cells including cardiomyocytes and vascular smooth muscle cells. These antagonistic actions may contribute to the pathogenesis of cardiovascular diseases and remodeling.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dzau VJ, Gibbons GH, Pratt RE. 1991. Molecular mechanism of vascular reninangiotensin system in mypintimal hyperplasia. Hypertension 18(Suppl II): 100–105.

    Google Scholar 

  2. Chiu AT, Herblin WF, McCall DE, Ardecky RJ, Carini DJ, Duncia JV, Pease LJ, Wong PC, Wexler RR, Johnson AL, Timmermans P. 1989. Identification of angiotensin II receptor subtypes. Biochem Biophys Res Commun 165:196–203.

    Article  PubMed  CAS  Google Scholar 

  3. Whitebread S, Mele M, Kamber B, de Gasparo M. 1989. Preliminary biochemical characterization of two angiotensin II receptor subtypes. Biochem Biophys Res Commun 163:284–291.

    Article  PubMed  CAS  Google Scholar 

  4. Sasaki K, Yamano Y, Bardhan S, Iwai N, Murray JJ, Hasegawa M, Matsuda Y, Inagami T. 1991. Cloning and expression of a complementary DNA encodoing a bovine adrenal angiotensin II type-1 receptor. Nature 351:230–233.

    Article  PubMed  CAS  Google Scholar 

  5. Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE. 1991. Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature 351:233–236.

    Article  PubMed  CAS  Google Scholar 

  6. Sasamura H, Hein L, Krieger JE, Pratt RE, Kobilka BK, Dzau VJ. 1992. Cloning, characterization, and expression of two angiotensin receptor (AT-1) isoforms from the mouse genome. Biochem Biophys Res Commun 185:253–259.

    Article  PubMed  CAS  Google Scholar 

  7. Inagami T, Guo DF, Kitami Y. 1994. Molecular biology of angiotensin II receptors: An overview. J Hypertens 12:S83–S94.

    CAS  Google Scholar 

  8. Grady EF, Sechi LA, Griffin CA, Schambelan M, Kalinyak JE. 1991. Expression of AT2 receptors in the developing rat fetus. J Clin Invest 88:921–933.

    Article  PubMed  CAS  Google Scholar 

  9. Millan MA, Jacobowitz DM, Aguilera G, Catt KJ. 1991. Differential distribution of AT1 and AT2 angiotensin II receptor subtypes in the rat brain during development. Proc Natl Acad Sci USA 88:11440–11444.

    Article  PubMed  CAS  Google Scholar 

  10. Pucell AG, Hodges JC, Sen I, Bumpus FM, Husain A. 1991. Biochemical properties of the ovarian granulosa cell type 2-angiotensin II receptor. Endocrinology 128:1947–1959.

    Article  PubMed  CAS  Google Scholar 

  11. Tsutsumi K, Saavedra JM. 1991. Characterization of AT2 angiotensin II receptors in rat anterior cerebral arteries. Am J Physiol 261:H667–H670.

    PubMed  CAS  Google Scholar 

  12. Tsutsumi K, Stromberg C, Viswanathan M, Saavedra JM. 1991. Angiotensin-II receptor subtypes in fetal tissues of the rat: Autoradiography, guanine nucleotide sensitivity, and association with phosphoinositide hydrolysis. Endocrinology 129:1075–1082.

    Article  PubMed  CAS  Google Scholar 

  13. Mukoyama M, Nakajima M, Horiuchi M, Sasamura H, Pratt RE, Dzau VJ. 1993. Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors. J Biol Chem 268:24539–24542.

    PubMed  CAS  Google Scholar 

  14. Kambayashi Y, Bardhan S, Takahashi K, Tsuzuki S, Inui H, Hamakubo T, Inagami T. 1993. Molecular cloning of a novel angiotensin II receptor isoform involved in phosphotyrosine phos-phatase inhibition. J Biol Chem 268:24543–24546.

    PubMed  CAS  Google Scholar 

  15. Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhang L, Horiuchi M, Pratt RE, Dzau VJ. 1995. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: Gain-of-function study using gene transfer. Proc Natl Acad Sci USA 92:10663–10667.

    Article  PubMed  CAS  Google Scholar 

  16. Yamada T, Horiuchi M, Dzau VJ. 1995. Mitogen-activated protein (MAP) kinase dephosphorylation by angiotensin II type 2 receptor induces apoptosis. Circulation 92:1–499.

    Article  Google Scholar 

  17. Yamada T, Horiuchi M, Dzau VJ. 1996. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA 93:156–160.

    Article  PubMed  CAS  Google Scholar 

  18. Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK. 1995. Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor gene in mice. Nature 377:744–747.

    Article  PubMed  CAS  Google Scholar 

  19. Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fugo A, Niimura F, Ichikawa I, Hogan BL, Inagami T. 1995. Effects on blood pressure and exploratory behavior of mice lavking angiotensin II type-2 receptor. Nature 377:748–750.

    Article  PubMed  CAS  Google Scholar 

  20. Stoll M, Steckelings M, Paul M, Bottari SP, Metzger R, Unger T. 1995. The angiotnsin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 95:651–657.

    Article  PubMed  CAS  Google Scholar 

  21. Booz GW, Baker KM. 1996. Role of typel and type2 angiotensin receptors in angiotensin receptors in angiotensin II-induced cardiomyocyte hypertrophy. Hypertension 28:635–640.

    Article  PubMed  CAS  Google Scholar 

  22. Koibuchi Y, Lee WS, Gibbons GH, Pratt RE. 1993. Role of transforming growth factor-beta 1 in the cellular growth response to angiotensin II. Hypertension 21:1046–1050.

    Article  PubMed  CAS  Google Scholar 

  23. Shanmugam S, Corvol P, Gasc J-M. 1996. Angiotensin II type 2 receptor mRNA expression in the developing cardiopulmonary system of the rat. Hypertension 28:91–97.

    Article  PubMed  CAS  Google Scholar 

  24. Daud AI, Bumpus FM, Husain A. 1988. Evidence for selective expression of angiotensin II receptors on atretic follicles in the rat ovary: An autoradiographic study. Endocrinology 122:2727–2734.

    Article  PubMed  CAS  Google Scholar 

  25. Cho A, Courtman DW, Langille BL. 1995. Apoptosis (programmed cell death) in arteries of the neonatal lamb. Circ Res 76:168–175.

    Article  PubMed  CAS  Google Scholar 

  26. Pollman M, Yamada M, Horiuchi M, Gibbons GH. 1996. Vasoactive substances rgulate smooth muscle cell apoptosis: Countervailing influences of nitric oxide and angiotensin II. Circ Res 79:748–756.

    Article  PubMed  CAS  Google Scholar 

  27. Hayashida W, Horiuchi M, Grandchamp J, Dzau VJ. 1996. Antagonistic action of angiotensin II type-1 and type-2 receptors on apoptosis in cultured neonatal rat ventricular myocytes. Hypertension 28:535.

    Google Scholar 

  28. Xia Z, Dickens M, Raingeard J, Davis RJ, Greenberg ME. 1995. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326–1331.

    Article  PubMed  CAS  Google Scholar 

  29. Horiuchi M, Hayashida W, Kambe T, Yamada T, Dzau VJ. 1996. Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis. J Biol Chem 272:19022–19026.

    Article  Google Scholar 

  30. Bennett MR, Evan GI, Newby AC. 1994. Deregulated expression of c-myc oncogene abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon-γ heparin, and cyclic nucleotide analogues and induces apoptosis. Circ Res 74:525–536.

    Article  PubMed  CAS  Google Scholar 

  31. Bennett MR, Evan GI, Schwartz SM. 1995. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest 95:2266–2274.

    Article  PubMed  CAS  Google Scholar 

  32. Isner JM, Kearney M, Bortman S, Passeri J. 1995. Apoptosis in human atherosclerosis and restenosis. Circulation 91:2703–2711.

    Article  PubMed  CAS  Google Scholar 

  33. Han DK, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. 1995. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol 147:267–277.

    PubMed  CAS  Google Scholar 

  34. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Lrajewski S, Reed JC, Olivetti G, Anversa P. 1996. Apoptotic and necrotic myocyte cell deaths are independent variables of infarct size in rats. Lab Invest 74:86–107.

    PubMed  CAS  Google Scholar 

  35. Nio Y, Matsubara H, Murasawa S, Kanasaki M, Inada M. 1995. Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. J Clin Invest 95:46–54.

    Article  PubMed  CAS  Google Scholar 

  36. Lopez JJ, Lorell BH, Ingelfinger JR, Weinberg EO, Schunkert H, Diamant D, Tang SS. 1994. Distribution and function of cardiac angiotensin AT1-and AT2-receptor subtypes in hypertrophied rat hearts. Am J Physiol 267:H844–H852.

    PubMed  CAS  Google Scholar 

  37. Brink M, de Gasparo M, Rogg H, Schmid A, Bullock G. 1995. Localization of the angiotensin II AT2 receptor subtype in the human heart. Circulation 92:1–63.

    Article  Google Scholar 

  38. Rogg H, de Gasparo M, Graedel E, Stulz P, Burkart F, Eberhard M, Erne P. 1996. Angiotensin-II receptor subtypes in human atria and evidence for alterations in patients with cardiac dysfunction. Eur Heart J 17:1112–1120.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiovascular Research, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA

    Masatsugu Horiuchi, Hiroyuki Yamada, Masahiro Akishita & Victor J Dzau

Authors
  1. Masatsugu Horiuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroyuki Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masahiro Akishita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Victor J Dzau
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla Ph.D., M.D. (Hon.) (Distinguished Professor and Director MRC Group in Experimental Cardiology), Peter Zahradka Ph.D. (Associate Professor), Ian M. C. Dixon Ph.D. (Assistant Professor) & Robert E. Beamish M.D. (Professor Emeritus) (Distinguished Professor and Director MRC Group in Experimental Cardiology),  (Associate Professor),  (Assistant Professor) &  (Professor Emeritus)

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Horiuchi, M., Yamada, H., Akishita, M., Dzau, V.J. (1998). Angiotensin II Regulated Apoptosis in Cardiovascular Remodeling. In: Dhalla, N.S., Zahradka, P., Dixon, I.M.C., Beamish, R.E. (eds) Angiotensin II Receptor Blockade Physiological and Clinical Implications. Progress in Experimental Cardiology, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5743-2_31

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5743-2_31

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7631-6

  • Online ISBN: 978-1-4615-5743-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation