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Summary

Angiotensinogen mRNA expression in human tissues was detected not only in the liver, but also in both atrial and ventricular heart tissues, suggesting that angiotensinogen is synthesized in the human heart. Angiotensinogen was present in the endocardial layer of the human left ventricle, rather than in the epicardial layer, and in the conduction system and right atrium. Furthermore, we found angiotensinogen to be widespread in the left ventricle of diseased hearts. We examined the involvement of collagen in the occurrence and progression of cardiomyopathy. In the early phase of cardiomyopathy, the extracellular matrix of the myocardium is rich in type III collagen, which is similar to immature tissues. In the later phase, the matrix resembles that of hard tissues in which collagen is mainly of type I and is insoluble. We also examined the relationship between angiotensin II and collagen synthesis. Previous studies have demonstrated that myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction in hypertensive cardiac hypertrophy. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats (SHR) was 1.6 fold greater than that in Wistar-Kyoto rats. The responsiveness of collagen production to angiotensin II was significantly enhanced in SHR. This effect was angiotensin receptor specific because it was blocked by the competitive inhibitor. These results indicate angiotensin II may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.

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References

  1. Robertson JIS, Nicholls MG (eds) (1993) The renin-angiotensin system. Gower, London

    Google Scholar 

  2. Garrison JC, Peach MJ (1990) Renin and angiotensin. In: Gilman AG, Rail TW, Nies AS, Taylor P (eds) The pharmacological basis of therapeutics. Pergamon, New York, pp 749–763

    Google Scholar 

  3. Kaplan NM, Lieberman E (1982) The renin-angiotensin system. In: Clinical hypertension. Williams & Wilkins, Baltimore, pp 210–232

    Google Scholar 

  4. Ohkubo H, Kageyama R, Ujihara M, Hirose T, Inayama S, Nakanishi S (1983) Cloning and sequence analysis of cDNA for rat angiotensinogen. Proc Natl Acad Sci USA 80:2196–2200

    Article  PubMed  CAS  Google Scholar 

  5. Kageyama R, Ohkubo H, Nakanishi S (1984) Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. Biochemistry 23:3603–3609.

    Article  PubMed  CAS  Google Scholar 

  6. Kunapuli SP, Kumar A (1987) Molecular cloning of human angiotensinogen cDNA and evidence for the presence of its mRNA in rat heart. Circ Res 60:786–790

    PubMed  CAS  Google Scholar 

  7. Panthier JJ, Foote S, Chambraud B, Strosberg AD, Corovol P, Rougeon F (1982) Complete amino acid sequence and maturation of the mouse submaxillary gland renin precursor. Nature (Lond) 298:90–92

    Article  CAS  Google Scholar 

  8. Imai T, Miyazaki H, Hirose S, Hori H, Hayashi T, Kageyama R, Ohkubo H, Nakanishi S, Murakami K (1983) Cloning and sequence analysis of cDNA for human renin precursor. Proc Natl Acad Sci USA 80:7405–7409

    Article  PubMed  CAS  Google Scholar 

  9. Ohkubo H, Nakayama K, Tanaka T, Nakanishi S (1986) Tissue distribution of rat angiotensinogen mRNA and structural analysis of its heterogeneity. J Biol Chem 261:319–323

    PubMed  CAS  Google Scholar 

  10. Dzau VJ, Ellison KE, Brody T, Ingelfinger J, Pratt RE (1987) A comparative study of the distribution of renin and angiotensinogen messenger ribonucleic acids in rat and mouse tissues. Endocrinology 120:2334–2338

    Article  PubMed  CAS  Google Scholar 

  11. Campbell DJ, Habener JF (1989) Hybridization in situ studies of angiotensinogen gene expression in rat adrenal and lung. Endocrinology 124:218–222

    Article  PubMed  CAS  Google Scholar 

  12. Dzau VJ (1987) Vascular angiotensin pathways. A new therapeutic target. J Cardiovasc Pharmacol 10(suppl 7):S9–S16

    Article  PubMed  CAS  Google Scholar 

  13. Khairallah PA, Robertson AL, Davila D (1972) Effect of angiotensin II on DNA, RNA and protein synthesis. In: Genest J, Koiw E (eds) Hypertension’ 72. Springer-Verlag, Berlin Heidelberg New York, pp 212–220

    Google Scholar 

  14. Dzau VJ (1987) Evolution of the clinical management of hypertension. Am J Med 82(suppl 1A):36–43

    Article  PubMed  CAS  Google Scholar 

  15. Li C, Prakash O, Re RN (1989) Altered regulation of angiotensin gene expression in the left ventricle of the hypertensive rats. Circulation 80:11450

    Google Scholar 

  16. Dzau VJ (1988) Cardiac renin-angiotensin system: molecular and functional aspect. Am J Med 84:22–27

    Article  PubMed  CAS  Google Scholar 

  17. Campbell DJ, Habener JF (1986) The angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest 78:31–39

    Article  PubMed  CAS  Google Scholar 

  18. Baker KM, Chemin MI, Wixson SK, Aceto JF (1990) Renin-angiotensin system involvement in pressure-overloaded cardiac hypertrophy in rats. Am J Physiol 259:H324–H332

    PubMed  CAS  Google Scholar 

  19. Drexler H, Lindpaintner K, Lu W, Schieffer B, Ganten D (1989) Transient increase in the expression of cardiac angiotensinogen in rat model of myocardial infarction and failure. Circulation 80:11459

    Article  Google Scholar 

  20. Sawa H, Tokuchi F, Mochizuki N, Endo Y, Furuta Y, Shinohara T, Takada A, Kawaguchi H, Yasuda H, Nagashima K (1992) Expression of the angiotensinogen gene and localization of its protein in the human heart. Circulation 86:138–146

    PubMed  CAS  Google Scholar 

  21. Mochizuki N, Sawa H, Yasuda H, Shinohara T, Nagashima K, Yamaji T, Ohnuma N, Hall WW (1991) Distribution of atrial natriuretic peptide in the conduction system and ventricular muscles of the human heart. Virchows Arch A Pathol Anat Histol 418:9–16

    Article  CAS  Google Scholar 

  22. Wharton J, Anderson R, Springall D, Power RF, Rose M, Smith A, Espejo R, Khaghani A, Wallwork J, Yacoub MH, Polak JM (1988) Localization of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart. Br Heart J 60:267–274

    Article  PubMed  CAS  Google Scholar 

  23. Sawa H, Mochizuki N, Kudo T, Kawaguchi H, Yasuda H, Tokuchi F, Nagashima K (1991) Increased angiotensinogen distribution in failing human hearts. Circulation 84(Suppl II):II441

    Google Scholar 

  24. Sawa H, Kawaguchi H, Mochizuki N, Endo Y, Kudo T, Tokuchi F, Fujioka Y, Nagashima K, Kitabatake A (1994) Distribution of angiotensinogen in diseased human heart. J Mol Biochem 132:15–23

    Article  CAS  Google Scholar 

  25. Matsubara H, Yamamoto J, Hirata Y, Mori Y, Oikawa S, Inada M (1990) Changes of atrial natriuretic peptide and its messenger RNA with development and regression of cardiac hypertrophy in renovascular hypertensive rats. Circ Res 66:176–184

    PubMed  CAS  Google Scholar 

  26. Jeunemaitre X, Soubrier F, Koteltev YU, Lifton RP, William CS, Charru A, Hunt SC, Hopkins PN, William RR, Lalouel J-M, Corvol P (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180

    Article  PubMed  CAS  Google Scholar 

  27. Weber KT, Brilla CG (1991) Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 83:1849–1865

    PubMed  CAS  Google Scholar 

  28. Allen IS, Cohen NM, Dhallan RS, Gaa ST, Lederer WJ, Rogers TB (1988) Angiotensin II increases spontaneous contractile frequency and stimulates calcium current in cultured neonatal rat heart myocytes: insights into the underlying biochemical mechanisms. Circ Res 62:524–534

    PubMed  CAS  Google Scholar 

  29. Saito K, Gutkind JS, Saavedra JM (1987) Angiotensin II binding sites in the conduction system of rat hearts. Am J Physiol 253:H1618–H1622

    PubMed  CAS  Google Scholar 

  30. Dzau VJ, Re RN (1987) Evidence for the existence of renin in the heart. Circulation 75(suppl I):I134–M36

    PubMed  CAS  Google Scholar 

  31. Klett CH, Hellmann W, Muller F, Suzuki F, Nakanishi S, Ohkubo H, Ganten D, Hackenthal E (1988) Angiotensin II controls angiotensinogen secretion at a pretranslational level. J Hypertens 6(suppl 4):S442–S445

    CAS  Google Scholar 

  32. Ganten D, Ganten U, Granger P, Boucher R, Genest J (1972) Renin in heart muscle and arterial tissue. Verh Dtsch Ges Kreislaufforsch 38:268

    Article  PubMed  CAS  Google Scholar 

  33. Re RN, Michalik RJ, Dzau VJ (1983) Cardiac myocytes contain renin. Clin Res 31:845A

    Google Scholar 

  34. Dzau VJ, Ellison KE, Onellete AJ (1985) Expression and regulation of renin in the mouse heart. Clin Res 33:181

    Google Scholar 

  35. Lindpainter K, Jin M, Wilhelm MJ, Suzuki F, Linz W, Schoelkens BA, Ganten D (1988) Intracardiac generation of angiotensin and its physiologic role. Circulation 77(suppl I):I18–I23

    Google Scholar 

  36. Field LJ, McGrowan R, Dickinson DP, Gross KW (1984) Tissue and gene specificity of mouse renin expression. Hypertension 6:597–603

    PubMed  CAS  Google Scholar 

  37. Dzau VJ, Ingelfinger J, Pratt RE, Ellison KE (1986) Identification of renin and angiotensin messenger RNA sequences in mouse and rat brains. Hypertension 8:544–548

    PubMed  CAS  Google Scholar 

  38. Ganten D, Ludwig G, Hennhoefer C (1986) Genetic control of renin in the tissues of different strains of mice. Naunyn-Schmiedebergs Arch Exp Pathol Pharmacol 332:R59

    Google Scholar 

  39. Suzuki F, Hellmann T, Murakami K, Ludwig G (1987) Expression of the genes for renin and angiotensinogen in tissues of rats. Naunyn-Schmiedebergs Arch Exp Pathol Pharmacol 335:R59

    Article  Google Scholar 

  40. Suzuki J, Matsubara H, Urakami M, Inada M (1993) Rat angiotensin II (type 1 A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. Circ Res 73:439–447

    PubMed  CAS  Google Scholar 

  41. Hirsh AT, Talsness CE, Schunkert H, Paul M, Dzau VJ (1991) Tissue-specific activation of cardiac angiotensinogen converting enzyme in experimental heart failure. Circ Res 69:475–482

    Google Scholar 

  42. Paul M, Wagner J, Dzau VJ (1993) Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction. J Clin Invest 91:2058–2064

    Article  PubMed  CAS  Google Scholar 

  43. Endo Y, Mochizuki N, Sawa H, Nagashima K, Ito K, Takamura I, Kawaguchi H (1992) Expression of angiotensinogen and renin mRNAs in the human heart. J Hypertens 10(Suppl 4):S73

    Google Scholar 

  44. Borg TK, Caulfield JB (1991) The collagen matrix of the heart. Fed Proc 40:2037–2041

    Google Scholar 

  45. Weber KT, Brilla CG (1991) Pathological hypertrophy and cardiac interstitium: fibrosis and renin-angiotensin-aldosterone system. Circulation 83:1849–1865

    PubMed  CAS  Google Scholar 

  46. Sen S, Bumpus FM (1979) Collagen synthesis in development and reversal of cardiac hypertrophy in spontaneously hypertensive rats. Am J Cardiol 44:954–958

    Article  PubMed  CAS  Google Scholar 

  47. Brilla CG, Janicki JS, Weber KT (1991) Cardioprotective effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy. Circulation 83:1771–1779

    PubMed  CAS  Google Scholar 

  48. Anversa P, Loud AV, Levicky V, Guideri G (1985) Left ventricular failure induced by myocardial infarction: I. Myocyte hypertrophy. Am J Physiol 248:H876–H882

    CAS  Google Scholar 

  49. Weisman HF, Bush DE, Mannis JA, Bulkley BH (1985) Global cardiac remodeling after myocardial infarction: a study in the rat model. J Am Coll Cardiol 5:1355–1362

    Article  PubMed  CAS  Google Scholar 

  50. Fletcher PJ, Pfeffer JM, Pfeffer MA, Braunwald E (1981) Left ventricular diastolic pressure-volume relations in rats with healed myocardial infarction. Circ Res 49:618–626

    PubMed  CAS  Google Scholar 

  51. Baker KM, Aceto JF (1990) Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol 259:H610–H618

    PubMed  CAS  Google Scholar 

  52. van Krimpen C, Smits JFM, Cleutjens JPM, Debets JJM, Schoemaker RG, Struyker HAJ, Bosman FT, Saemen MJAP (1991) DNA synthesis in the non-infarcted cardiac interstitium after left coronary artery ligation in the rat: effects of captoril. J Mol Cell Cardiol 123:1245–1253

    Article  Google Scholar 

  53. Weber KT, Janicki JS (1989) Angiotensin and the remodeling of the myocardium. Br J Clin Pharmacol 28:141S–150S

    PubMed  CAS  Google Scholar 

  54. Eghbali M, Czaja MK, Zeydel M, Weiner FR, Zern MA, Seifter S (1988) Collagen chain mRNAs in isolated heart cells from young and adult rats. J Mol Cell Cardiol 20:267–276

    Article  PubMed  CAS  Google Scholar 

  55. Sano H, Okada H, Kawaguchi H, Yasuda H (1991) Increased angiotensin II-stimulated collagen synthesis in cultured fibroblasts from spontaneously hypertensive rats. Circulation 84 (suppl II):II48

    Google Scholar 

  56. Geisterfer AAT, Peach MJ, Owens GK (1988) Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 62:749–756

    PubMed  CAS  Google Scholar 

  57. Naftilan AJ, Pratt RE, Dzau VJ (1989) Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured vascular smooth muscle cells. J Clin Invest 83:1419–1424

    Article  PubMed  CAS  Google Scholar 

  58. Kawahara Y, Sunako M, Tsuda T, Fukuzaki H, Fukumoto Y, Takai Y (1988) Angiotensin II induces expressions of the c-fos gene through protein kinase C activation and calcium ion mobilization. Biochem Biophys Res Commun 150:52–59

    Article  PubMed  CAS  Google Scholar 

  59. Naftilan AJ, Gilliland GK, Eldridge CS, Kraft AS (1990) Induction of the protooncogene c-jun by angiotensin II Mol Cell Biol 10:5536–5540

    PubMed  CAS  Google Scholar 

  60. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS (1986) Transforming growth factor type B: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83:4167–171

    Article  PubMed  CAS  Google Scholar 

  61. Eghbali M, Tomek R, Sukhatme VP, Woods C, Bhambi B (1991) Differential effects of transforming growth factor-β1and phorbol myristate acetate on cardiac fibroblasts: regulation of fibrillar collagen mRNA and expression of early transcription factors. Circ Res 69:483–490

    PubMed  CAS  Google Scholar 

  62. 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 

  63. Wong PC, Price WA, Chiu AT, Duncia JV, Carini DJ, Wexler RR, Johnson AL, Timmermans PBWM (1989) Nonpeptide angiotensin II receptor antagonists. IX. Antihypertensive activity in rats: DuP753, an orally active antihypertensive. J Pharmacol Exp Ther 252:726–732

    Google Scholar 

  64. 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 

  65. Sadoshima J, Izumo S (1993) Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res 73:413–423

    PubMed  CAS  Google Scholar 

  66. Bajusz E (1969) Hereditary cardiomyopathy: a new disease model. Am Heart J 77:686–696

    Article  PubMed  CAS  Google Scholar 

  67. Strobeck JE, Factor SM, Bhan A, Sole M, Liew CC, Fein F, Sonnenblick EH (1979) Hereditary and acquired cardiomyopathies in experimental animals: mechanical, biochemical, and structural features. Ann NY Acad Sci 317:59–88

    PubMed  CAS  Google Scholar 

  68. Homburger F, Baker JR, Nixon CW, Whitney R (1962) Primary generalized polymyopathy and cardiac necrosis in an inbred line of Syrian hamsters. Med Exp 6:339–345

    Google Scholar 

  69. Bajusz E, Baker JR, Nixon CW, Homburger F (1969) Spontaneous hereditary myocardial degeneration and congestive heart failure in a strain of Syrian hamsters. Ann NY Acad Sci 156:105–129

    Article  PubMed  CAS  Google Scholar 

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© 1998 Springer-Verlag Tokyo

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Kawaguchi, H., Kitabatake, A. (1998). Molecular Mechanism of Cardiovascular Remodeling. In: Abiko, Y., Karmazyn, M. (eds) Protection Against Ischemia/Reperfusion Damage of the Heart. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68482-4_9

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  • DOI: https://doi.org/10.1007/978-4-431-68482-4_9

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