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Functional Analysis of Tissue Renin-Angiotensin System Using “Gain and Loss of Function” Approaches: In Vivo Test of in Vitro Hypothesis

  • Chapter
Angiotensin II Receptor Blockade Physiological and Clinical Implications

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

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Summary

The study of the effect of autocrine-paracrine vasoactive modulators (e.g., renin-angiotensin) on VSMC biology is very difficult in vivo because in vivo studies are limited. Recent progress in in vivo gene transfer technologies have provided us with the opportunity to study cellular responses to the manipulation of the individual components (i.e., by overexpression or inhibition). Currently, many researchers have developed many in vivo gene transfer techniques for cardiovascular application, including viral gene transfer and liposomal gene transfer. By using in vivo gene transfer approaches, the roles of the tissue renin-angiotensin system have been identified. Such an approach may increase our understanding of the biology and pathobiology of autocrine-paracrine system. This review has discussed the potential utility of in vivo gene transfer methods.

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References

  1. Morishita R, Gibbons GH, Ellison KE, Lee W, Zhang L, Kaneda Y, Ogihara T, Dzau VJ. 1994. Evidence for direct local effect of angiotensin in vascular hypertrophy: in vivo gene transfer of angiotensin converting enzyme. J Clin Invest 94:978–984.

    Article  PubMed  CAS  Google Scholar 

  2. Tomita N, Morishita R, Higaki J, Aoki M, Nakamura Y, Mikami H, Fukamizu A, Murakami K, Kaneda Y, Ogihara T. 1995. Transient decrease in high blood pressure by in vivo transfer of antisense oligodeoxynucleotides against rat angiotensinogen. Hypertension 26:131–136.

    Article  PubMed  CAS  Google Scholar 

  3. Morishita R, Higaki J, Tomita N, Aoki M, Moriguchi A, Tamura K, Murakami K, Kaneda Y, Ogihara T. 1996. Role of transcriptional cis-elements, angiotensinogen gene-activating element, of angiotensinogen gene in blood pressure regulation. Hypertension 27:502–507.

    Article  PubMed  CAS  Google Scholar 

  4. Morishita R, Higaki J, Aoki M, Hayashi S, Kida I, Kaneda Y, Ogihara T. 1996. Novel strategy of gene therapy in cardiovascular disease with HVJ-liposome method. In Progression of chronic renal diseases, Ed. H Koide Contrib Nephrol 118:254–264.

    CAS  Google Scholar 

  5. Morishita R, Gibbons GH, Dzau VJ. 1993. Gene therapy as potential treatment for cardiovascular diseases. In Cardiovascular pharmacology And therapeutics. Ed. Singh BN, 51–61. New York: Libingstone Publisher.

    Google Scholar 

  6. Cepko CL, Roberts BE, Mulligan RC. 1994. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell 37:1053.

    Article  Google Scholar 

  7. Kaneda Y, Morishita R, Tomita N. 1995. Increased expression of DNA cointroduced with nuclear protein in adult rat liver. J Mol Med 73:289–297.

    Article  PubMed  CAS  Google Scholar 

  8. Yonemitsu Y, Kaneda Y, Morishita R, Nakagawa K, Nakashima Y, Sueishi K. 1996. Characterization of in vivo gene transfer into the arterial wall mediated by the Sendai virus (Hemagglutinating Virus of Japan) liposomes: An effective tool for the in vivo study of arterial diseases. Lab Invest 75:313–323.

    PubMed  CAS  Google Scholar 

  9. Dzau VJ, Mann MJ, Morishita R, Kaneda Y. 1996. Fusigenic viral liposome for gene therapy in cardiovascular diseases. Proc Natl Acad Sci USA 93:11421–11425.

    Article  PubMed  CAS  Google Scholar 

  10. Kaneda Y, Iwai K, Uchida T. 1989. Increased expression of DNA cointroduced with nuclear protein in adult rat liver. Science 243:375–378.

    Article  PubMed  CAS  Google Scholar 

  11. Morishita R, Gibbons GH, Ellison KE, Nakajima M, Leyen HVL, Zhang L, Kaneda Y, Ogihara T, Dzau VJ. 1994. Intimai hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides. Journal of Clinical Investigation 93:1458–1464.

    Article  PubMed  CAS  Google Scholar 

  12. Morishita R, Gibbons GH, Kaneda Y, Ogihara T, Dzau VJ. 1994. Pharmacokinetics of antisense oligonucleotides (cyclin B1 and ede 2 kinase) in the vessel wall: Enhanced therapeutic utility for restenosis by HVJ-liposome method. Gene 149:13–19.

    Article  PubMed  CAS  Google Scholar 

  13. Lim CS, Chapman GD, Gammon RS, Muhlestein JB, Bauman RP, Stack RS, Swain JL. 1991. Direct in vivo gene transfer into the coronary and peripheral vascultures of the intact dog. Circulation 83:2007–2011.

    Article  PubMed  CAS  Google Scholar 

  14. Mullins JJ, Peters J, Ganten D. 1990. Fulminant hypertension in transgenic rats harboring the mouse Ren-2 gene. Nature 344:541–544.

    Article  PubMed  CAS  Google Scholar 

  15. Dzau VJ, Gibbons GH, Morishita R, Pratt E. 1994. New perspectives in hypertension research: potentials of vascular biology. Hypertension 23:1132–1140.

    Article  PubMed  CAS  Google Scholar 

  16. Dzau VJ, Brody T, Ellison KE, Pratt RE, Ingelfinger JR. 1987. Tissue-specific regulation of renin expression in the mouse. Hypertension 9:36–41.

    Google Scholar 

  17. Field LJ, McGowan RA, Dickinson DP, Gross KW. 1984. Tissue and gene specificity of mouse renin expression. Hypertension 6:597–603.

    Article  PubMed  CAS  Google Scholar 

  18. Dzau VJ, Burt DW, Pratt RE. 1988. Molecular biology of the renin angiotensin system. Am J Physiol 255:F563–F573.

    PubMed  CAS  Google Scholar 

  19. Samani NJ, Swales JD, Brammar WJ. 1989. A widespread abnormality of renin gene expression in the spontaneously hypertensive rat: Modulation in some tissues with the development of hypertension. Clin Sci 77:629–636.

    PubMed  CAS  Google Scholar 

  20. Tomita N, Higaki J, Kaneda Y, Yu H, Morishita R, Mikami H, Ogihara T. 1993. Hypertensive rats produced by in vivo introduction of the human renin gene. Circulation Research 73:898–905.

    Article  PubMed  CAS  Google Scholar 

  21. Re RN, Fallon JT, Dzau VJ, Quay S, Haber E. 1982. Renin synthesis by canine aortic smooth muscle cells in culture. Life Sci 30:99–106.

    Article  PubMed  CAS  Google Scholar 

  22. Morishita R, Higaki J, Miyazaki M, Ogihara T. 1992. Possible role of the vascular renin angiotensin system in hypertension and vascular hypertrophy. Hypertension 19:II-62-II-67.

    Google Scholar 

  23. Okamura T, Miyazaki M, Inagami T, Toda N. 1986. Vascular renin angiotensin system in two-kidney, one clip hypertensive rats. Hypertension 8:560–565.

    Article  PubMed  CAS  Google Scholar 

  24. Mendelsohn FAO. 1985. Localization and properties of angiotensin receptors. J Hypertens 3:307–316.

    Article  PubMed  CAS  Google Scholar 

  25. Rakugi H, Jacob HJ, Krieger JE, Ingelfinger JR, Pratt RE. 1993. Vascular injury induces angiotensinogen gene expression in the media and neointima. Circulation 87:283–290.

    Article  PubMed  CAS  Google Scholar 

  26. Rakugi H, Kim DK, Krieger JE, Wang DS, Dzau VJ, Pratt RE. 1994. Induction of angiotensin converting enzyme in the neointima after vascular injury: possible role in restenosis. J Clin Invest 93:339–346.

    Article  PubMed  CAS  Google Scholar 

  27. Nakajima M, Hutchinson H, Fujinaga M, Hayashida W, Morishita R, Zhang L, Horiuchi M, Pratt RE, Dzau VJ. 1995. The 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 

  28. 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 

  29. Sawa Y, Suzuki K, Bai HZ, Shirakura R, Morishita R, Kaneda Y, Matsuda H. 1995. Efficiency of in vivo gene transfection into transplanted rat heart by coronary infusion of HVJ-liposome. Circulation 92:II-479-II-482.

    Google Scholar 

  30. Aoki M, Morishita R, Higaki J, Moriguchi A, Hayashi S, Matsushita H, Kida I, Tomita N, Sawa Y, Kaneda Y, Ogihara T. 1997. Survival of grafts of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and ß-galactosidase gene in non-infarcted area, but not myocardial infarcted area. Gene Therapy 4:120–127.

    Article  PubMed  CAS  Google Scholar 

  31. Aoki M, Morishita R, Higaki J, Moriguchi A, Kida I, Hayashi S, Matsushita H, Kaneda Y, Ogihara T. 1997. In vivo transfer efficiency of antisense oligonucleotides into the myocardium using HVJ-liposome method. Biochemical Biophysics Research Communication 231:540–545.

    Article  CAS  Google Scholar 

  32. Aoki M, Morishita R, Muraishi A, Moriguchi A, Sugimoto T, Maeda K, Dzau VJ, Kaneda Y, Higaki J, Ogihara T. 1997. Efficient in vivo gene transfer into heart in rat myocardial infarction model using HVJ (Hemagglutinating Virus of Japan)-liposome method. J Mol Cell Cardiol 29:949–959.

    Article  PubMed  CAS  Google Scholar 

  33. Lin H, Parmacek MS, Morle G, Boiling S, Leiden JM. 1990. Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation. 82:2217–2221.

    Article  PubMed  CAS  Google Scholar 

  34. Buttric PM, Kass A, Kitsis RN, Kaplan MR, Lainwand LA. 1992. Behavior of genes directly injected into the rat heart in vivo. Circ Res 70:193–198.

    Article  Google Scholar 

  35. Harsdorf RV, Schott RJ, Shen Y-T, Vatner SF, Mahdavi V, Ginard BN. 1993. Gene injection into canine myocardium as a useful model for studying gene expression in the heart of large mammals. Circ Res 72:688–695.

    Article  Google Scholar 

  36. Gal D, Weir L, Leclerc G, Pickering JG, Hogan J, Isner JM. 1993. Direct myocardial transfection in two animal models evaluation of parameters affecting gene expression and percutaneous gene delivery. Lab Invest 68:18–25.

    PubMed  CAS  Google Scholar 

  37. Schneider MD, French BA. 1993. The advent of adenovirus gene therapy for cardiovascular disease. Circulation 88:1937–1942.

    Article  PubMed  CAS  Google Scholar 

  38. Kirshenbaum LA, MacLellan WR, Mazur W, French BA, Schneider MD. 1993. Highly efficient gene transfer into adult ventricular myocytes by recombinant adenovirus. J Clin Invest 92:381–387.

    Article  PubMed  CAS  Google Scholar 

  39. Guzman RJ, Lemarchand P, Crystal RG, Epstein SE, Finke T. 1993. Efficient gene transfer into myocardium by direct injection of adenovirus vectors. Circ Res 73:1202–1207.

    Article  PubMed  CAS  Google Scholar 

  40. French BA, Mazur W, Geske RS, Bolli R. 1994. Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. Circulation 90:2414–2424.

    Article  PubMed  CAS  Google Scholar 

  41. Barr E, Carroll JC, Kalynych AM, Tripathy SK, Kozarski K, Wilson JM, Leiden JM. 1994. Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus. Gene Therapy 1:51–58.

    PubMed  CAS  Google Scholar 

  42. Xu H, Miller J, Liang BT. 1992. High-efficiency gene transfer into cardiac myocytes. Nucleic Acids Res 20:6425–6426.

    Article  PubMed  CAS  Google Scholar 

  43. Jeunematire X, Soubrier F, Kotelevetsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, Corvol P. 1992. Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180.

    Article  Google Scholar 

  44. Caulfield M, Lavender P, Farrall M, Munroe P, Lawson M, Turner P, Clark A. 1994. Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 330:1629–1633.

    Article  PubMed  CAS  Google Scholar 

  45. Akhtar S, Juliano RL. 1992. Cellular uptake and intracellular fate of antisense oligonucleotides. Trends in Cell Biol 2:139–144.

    Article  CAS  Google Scholar 

  46. Tomita N, Morishita R, Higaki J, Tomita S, Aoki M, Kaneda Y, Ogihara T. 1995. Role of angiotensinogen in blood pressure regulation in normotensive rats: Application of a “loss of function” approach. J Hypertens 13:1767–1774.

    Article  PubMed  CAS  Google Scholar 

  47. Tamura K, Umehara S, Ishii M, Tanimoto K, Murakami K, Fukamizu A. 1994. Molecular mechanism of transcriptional activation of angiotensinogen gene by proximal promoter. J Clin Invest 93:1370–1379.

    Article  PubMed  CAS  Google Scholar 

  48. Morishita R, Gibbons GH, Horiuchi M, Ellison KE, Nakajima M, Zhang L, Kaneda Y, Ogihara T, Dzau VJ. 1995. A novel molecular strategy using cis element “decoy” of E2F binding site inhibits smooth muscle proliferation in vivo. Proc Natl Acad Sci 92:5855–5859.

    Article  PubMed  CAS  Google Scholar 

  49. Yamada T, Horiuchi M, Morishita R, Zhang L, Pratt RE, Dzau VJ. 1995. In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer. J Clin Invest 96:1230–1237.

    Article  PubMed  CAS  Google Scholar 

  50. Bielinska A, Shivdasani RA, Zhang L, Nabel GJ. 1990. Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science 250:997–1000.

    Article  PubMed  CAS  Google Scholar 

  51. Sullenger BA, Gallardo HF, Ungers GE, Giboa E. 1990. Overexpression of TAR sequence renders cells resistant to human immunodeficiency virus replication. Cell 63:601–608.

    Article  PubMed  CAS  Google Scholar 

  52. Yamada K, Moriguchi A, Morishita R, Kaneda Y, Mikami H, Higaki J, Ogihara T. 1996. Importance of transcriptional cis-element of angiotensinogen in the central regulation of blood pressure (abstract). Hypertension 28:521.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Geriatric Medicine, Osaka University Medical School, Osaka, Japan

    Ryuichi Morishita, Motokuni Aoki, Hidetsugu Matsushita, Shin-Ichiro Hayashi, Shigefumi Nakamura, Nobuaki Nakano, Tadahiko Nishii, Kei Yamamoto, Naruya Tomita, Atsushi Moriguchi, Jitsuo Higaki & Toshio Ogihara

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  1. Ryuichi Morishita
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  2. Motokuni Aoki
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  3. Hidetsugu Matsushita
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  4. Shin-Ichiro Hayashi
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  5. Shigefumi Nakamura
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  6. Nobuaki Nakano
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  12. Toshio Ogihara
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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)

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Morishita, R. et al. (1998). Functional Analysis of Tissue Renin-Angiotensin System Using “Gain and Loss of Function” Approaches: In Vivo Test of in Vitro Hypothesis. 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_14

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  • DOI: https://doi.org/10.1007/978-1-4615-5743-2_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7631-6

  • Online ISBN: 978-1-4615-5743-2

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