Molecular and Cellular Biochemistry

, Volume 96, Issue 1, pp 1–14 | Cite as

Collagen and the myocardium: fibrillar structure, biosynthesis and degradation in relation to hypertrophy and its regression

  • Mahboubeh Eghbali
  • Karl T. Weber
Invited Paper

Abstract

The extracellular matrix of the myocardium contains an elaborate structural matrix composed mainly of fibrillar types I and III collagen. This matrix is responsible for the support and alignment of myocytes and capillaries. Because of its alignment, location, configuration and tensile strength, relative to cardiac myocytes, the collagen matrix represents a major determinant of myocardial stiffness. Cardiac fibroblasts, not myocytes, contain the mRNA for these fibrillar collagens. In the hypertrophic remodeling of the myocardium that accompanies arterial hypertension, a progressive structural and biochemical remodeling of the matrix follows enhanced collagen gene expression. The resultant significant accumulation of collagen in the interstitium and around intramyocardial coronary arteries, or interstitial and perivascular fibrosis, represents a pathologic remodeling of the myocardium that compromises this normally efficient pump. This report reviews the structural nature, biosynthesis and degradation of collagen in the normal and hypertrophied myocardium. It suggests that interstitial heart disease, or the disproportionate growth of the extracellular matrix relative to myocyte hypertrophy, is an entity that merits greater understanding, particularly the factors regulating types I and III collagen gene expression and their degradation.

Key words

type I and III collagen fibrosis hypertension collagen gene expression collagen degradation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Weber KT, Clark WA, Janicki JS, Shroff SG: Physiologic versus pathologic hypertrophy and the pressure-overload myocardium. J Cardiovasc Pharm 10: S37-S49, 1987Google Scholar
  2. 2.
    Weber KT, Janicki JS, Shroff SG, Pick R, Abrahams C, Chen RM, Bashey RI: Collagen compartment remodeling in the pressure overloaded left ventricle. J Appl Cardiol 3: 37–46, 1988Google Scholar
  3. 3.
    Weber KT: Cardiac interstitium in health and disease: The fibrillar collagen network. J Am Coll Cardiol 13: 1637–1652, 1989Google Scholar
  4. 4.
    Caulfield JB, Borg TK: The collagen network of the heart. Lab Invest 40: 364–372, 1979Google Scholar
  5. 5.
    Robinson TF, Cohen-Gould L, Factor SM: Skeletal framework of mammalian heart muscle. Lab Invest 49: 482–498, 1983Google Scholar
  6. 6.
    Robinson TF, Cohen-Gould L, Factor SM, Eghbali M, Blumenfeld OO: Structure and function of connective tissue in cardiac muscle: Collagen types I and III in endomysial struts and pericellular fibers. SEM 2: 1005–1015, 1988Google Scholar
  7. 7.
    Robinson TF, Geraci MA, Sonnenblick EH, Factor SM: Coiled perimysial fibers of papillary muscle in rat heart: Morphology, distribution, and changes in configuration. Circ Res 63: 577–592, 1988Google Scholar
  8. 8.
    Borg TK, Ranson WF Moshlehy, FA, Caulfield JB: Structural basis of ventricular stiffness. Lab Invest 44:49–54, 1981Google Scholar
  9. 9.
    Factor SM, Robinson TF: Comparative connective tissue structure — function relationships in biologic pumps. Lab Invest 58: 150–156, 1988Google Scholar
  10. 10.
    Kovanen V, Sudminen H, Heikkinen E: Connective tissue of ‘fast’ and ‘slow’ skeletal muscle in rats. Effects of endurance training. Acta Physiol Scand 108: 173–180, 1980Google Scholar
  11. 11.
    Horowitz A, Lanir Y, Yin FC, Perl M, Sheinman I, Strumpf RK: Structural three-dimensional constitutive law for the passive myocardium. J Biomech Eng 110: 200–207, 1988PubMedGoogle Scholar
  12. 12.
    Ohayon J, Chadwick RS: Effects of collagen microstructure on the mechanics of the left ventricle. Biophys J 54: 1077–1088, 1988Google Scholar
  13. 13.
    Borg TK, Sullivan T, Ivy J: Functional arrangement of connective tissue in striated muscle with emphasis on cardiac muscle. SEM 4: 1775–1784, 1982Google Scholar
  14. 14.
    Iwazumi T, ter Keurs HEDJ: Mechanical properties of single cardiac myocytes and ultra small trabeculae of rat (Abstr). Circulation 76: IV-331, 1987Google Scholar
  15. 15.
    Bing OHL, Matsushita S, Fanburg BL, Levine HJ: Mechanical properties of rat cardiac muscle during experimental hypertrophy. Circ Res 28: 233–245, 1971Google Scholar
  16. 16.
    Bing OHL, Fanburg BL, Brooks WW, Matsushita S: The effect of the lathyrogen β-amino proprionitrile (BAPN) on the mechanical properties of experimentally hypertrophied rat cardiac muscle. Circ Res 43: 632–637, 1978Google Scholar
  17. 17.
    Weber KT, Janicki JS, Shroff SG, Pick R, Chen RM, Bashey RI: Collagen remodeling of the pressure overloaded, hypertrophied nonhuman primate myocardium. Circ Res 62: 757–765, 1988Google Scholar
  18. 18.
    Doering CW, Jalil JE, Janicki JS, Pick R, Aghili S, Abrahams C, Weber KT: Collagen network remodeling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophy. Cardiovasc Res 22: 686–695, 1988Google Scholar
  19. 19.
    Jalil JE, Doering CW, Janicki JS, Pick R, Shroff S, Weber KT: Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle. Circ Res 64: 1041–1050, 1989Google Scholar
  20. 20.
    Abrahams C, Janicki JS, Weber KT: Myocardial hypertrophy in Macaca fascicularis: structural remodeling of the collagen matrix. Lab Invest 56: 676–683, 1987Google Scholar
  21. 21.
    Carroll EP, Janicki JS, Jalil JE, Shroff SG, Pick R, Weber KT: Myocardial stiffness and reparative fibrosis following coronary embolization. Cardiovasc Res 23: 655–661, 1989Google Scholar
  22. 22.
    Jalil JE, Janicki JS, Pick R, Abrahams C, Weber KT: Fibrosis-induced reduction of endomyocardium in the rat after isoproterenol treatment. Circ Res 65: 258–264, 1989Google Scholar
  23. 23.
    Medugorac I, Jacob R: Characterization of left ventricular collagen in the rat. Cardiovasc Res 17: 15–21, 1983Google Scholar
  24. 24.
    Eghbali M, Czaja MJ, Zeyel M, Weiner FR, Zern MA, Seifter S, Blumenfeld OO: Collagen mRNAs in isolated adult heart cells. J Mol Cell Cardiol 20: 267–276, 1988Google Scholar
  25. 25.
    Eghbali M, Blumenfeld OO, Seifter S, Buttrick PM, Leinwand LA, Robinson TF, Zern MA, Giambrone MA: Localization of types I, III, and IV collagen mRNAs in rat heart cells by in situ hybridization. J Mol Cell Cardiol 21: 103–113, 1989Google Scholar
  26. 26.
    Brutsaert DL, Meulemans AL, Sipido KR, Sys SU: Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle: Circ Res 62: 358–366, 1988Google Scholar
  27. 27.
    Pick R, Jalil JE, Janicki JS, Weber KT: The fibrillar nature and structure of isoproterenol-induced myocardial fibrosis in the rat. Am J Pathol 134: 365–371, 1989Google Scholar
  28. 28.
    Pick R, Janicki JS, Weber KT: Myocardial fibrosis in nonhuman primate with pressure overload hypertrophy. Am J Pathol 135: 771–781, 1989Google Scholar
  29. 29.
    Burton AC: Relation of structure to function of the tissues of the wall of blood vessels. Physiol Rev 34: 619–642, 1954PubMedGoogle Scholar
  30. 30.
    Parry DAD, Craig AS: Collagen fibrils during development and maturation and their contribution to the mechanical attributes of connective tissue. In: ME Nimni (ed) Collagen. CRC Press, Inc, Boca Raton, 1988 pp 1–23Google Scholar
  31. 31.
    Weber KT, Janicki JS, Pick R: Disruption of collagen tethers: Anatomic basis of muscle fiber slippage in the myocardium. Proceedings of Johannes Linzbach Symposium on Ventricular Dilatation. (In press), 1990Google Scholar
  32. 32.
    Linzbach AJ: Heart failure from the point of view of quantitative anatomy. Am J Cardiol 5: 370–382, 1960Google Scholar
  33. 33.
    Robinson TF, Factor SM, Capasso JM, Wittenberg BA, Blumenfeld OO: Morphology, composition and function of struts between cardiac myocytes of rat and hamster. Cell Tissue Res 249: 247–255, 1987Google Scholar
  34. 34.
    Terracio L, Borg TK: Factors affecting cardiac cell shape. Heart Failure 4: 114–124, 1988Google Scholar
  35. 35.
    Winegrad S, Robinson TF: Force generation among cells in the relaxing heart. Eur J Cardiol 7: 63–70, 1978Google Scholar
  36. 36.
    Ramirez F, Bernard M, Chu ML, Dickson L, deWet W, Junien C, Sobel M: Isolation and characterization of the human fibrillar collagen genes. Ann NY Acad Med 460: 117–129, 1985Google Scholar
  37. 37.
    Boedtker H, Finer M, Alto S: The structure of the chicken α2 collagen gene. Ann NY Acad Med 460: 85–116, 1985Google Scholar
  38. 38.
    deCrombrugghe B, Schmidt A, Liau G, Setoyama C, Mudryj M, Yoshihiko Y, McKeon C: Structural and functional analysis of genes for α2 (II) and α1 (III) collagens. Ann NY Acad Med 460: 154–162, 1985Google Scholar
  39. 39.
    Upholt WB, Strom CM, Sandell LJ: Structure of type II collagen gene. Ann NY Acad Med 460: 130–140, 1985Google Scholar
  40. 40.
    Pihlazaniemi T, Tryggvason K, Myers JC, Kurknien M, Lebo R, Cheung MC, Prokop D, Boyd CD: cDNA clones cloding for pro α1 (IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two levels of the carboxyl-terminal demain. J Biol Chem 260: 7681–7687, 1985Google Scholar
  41. 41.
    Raghow R, Thompson JP: Molecular mechanisms of collagen gene expression. Mol Cell Biochemistry 86: 5–18, 1989Google Scholar
  42. 42.
    Nair KG, Cutilletta AF, Zak R, Koide T, Rabinowitz M: Biochemical correlates of cardiac hypertrophy. I. Experimental model; changes in heart weight, RNA content, and nuclear RNA polymerase activity. Circ Res 23: 451–462, 1968Google Scholar
  43. 43.
    Schreiber SS, Oratz M, Evans CD, Gueyikian I, Rothschild MA: Myosin, myoglobin, and collagen synthesis in acute cardiac overload. Am J Physiol 219: 481–486, 1970Google Scholar
  44. 44.
    Koide T, Rabinowitz M: Biochemical correlates of cardiac hypertrophy. II. Increased rate of RNA synthesis in experimental cardiac hypertrophy in the rat. Circ Res 24: 9–18, 1969Google Scholar
  45. 45.
    Posner BI, Fanburg BL: Studies on components of RNA in cardiac muscle with emphasis on the rapidly labelled 4 to 18s fraction. Circ Res 19: 805–815, 1966Google Scholar
  46. 46.
    Izumo S, Nadal-Ginard B, Mahdavi V: Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci 85: 339–343, 1988Google Scholar
  47. 47.
    Starksen NF, Simpson PC, Bishopric N, Coughlin SR, Lee WMF, Escobedo JA, Williams LT: Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. Proc Natl Acad Sci 83: 8348–8350, 1986Google Scholar
  48. 48.
    Lindy S, Turto H, Uitto J: Protocollagen proline hydroxylase activity in rat heart during experimental cardiac hypertrophy. Circ Res 30: 205–209, 1972Google Scholar
  49. 49.
    Turto H: Collagen metabolism in experimental cardiac hypertrophy in the rat and effect of digitoxin treatment. Cardiovasc Res 11: 358–366, 1977Google Scholar
  50. 50.
    Morkin E, Ashford TP: Myocardial DNA synthesis in experimental cardiac hypertrophy. Am J Physiol 215: 1409–1413, 1968Google Scholar
  51. 51.
    Bonnin CM, Sparrow MP, Taylor RR: Collagen synthesis and content in right ventricular hypertrophy in the dog. Am J Physiol 10: 14703–14713, 1981Google Scholar
  52. 52.
    Turner JE, Oliver MH, Guerreiro D, Laurent GJ: Collagen metabolism during right ventricular hypertrophy following induced lung injury. Am J Physiol 21: 14915–14919, 1986Google Scholar
  53. 53.
    Chapman D, Weber KT, Eghbali M: Accumulation and localization of types I and III collagen in the hypertrophied rat left ventricle. (Abstr). FASEB 3: A621, 1989Google Scholar
  54. 54.
    Chapman D, Weber KT, Eghbali M: Regulation of collagen types I and III gene expression in the hypertrophied rat myocardium. (Abstr). Circulation 80: II-457, 1989Google Scholar
  55. 55.
    Laurent GJ, Sparrow MP, Bates PC, Millward DJ: Turnover of muscle protein in the fowl: Collagen content and turnover in cardiac and skeletal muscles of the adult fowl and the changes during stretch-induced growth. Biochem J 176:419–427, 1978Google Scholar
  56. 56.
    Caspari PG, Gibson K, Harris P: Changes in myocardial collagen in normal development and after β blockade. Rec Adv Card Struc Metab 7: 99–104, 1976Google Scholar
  57. 57.
    Eghbali ME, Eghbali M, Robinson TF, Seifter S, Blumenfeld OO: Collagen accumulation in heart ventricles as a function of growth and aging. Cardiovasc Res 23: 723–729, 1989Google Scholar
  58. 58.
    Dawson R, Milne G, Williams RB: Changes in the collagen of rat heart in cooper-deficiency-induced cardiac hypertrophy. Cardiovasc Res 16: 559–565, 1982Google Scholar
  59. 59.
    Shields GS, Coulson WF, Kimball DA, Carnes WH, Cartwright GE, Wintrobe MM: Studies on copper metabolism. XXXII. Cardiovascular lesions of copper-deficient swine. Am J Pathol 41: 603–621, 1962Google Scholar
  60. 60.
    Weber KT, Pick R, Janicki JS, Gadodia G, Lakier JB: Inadequate collagen tethers in dilated cardiopathy. Am Heart J 116: 1641–1646, 1988Google Scholar
  61. 61.
    Werb Z, Burleigh MC: A specific collagenase from rabbit fibroblasts in monolayer culture. Biochem J 137: 373–385, 1974Google Scholar
  62. 62.
    Dayer JM, Graham R, Russel G, Krane SM: Collagenase production by rheumatoid synovial cells: Stimulation by a human lymphocyte factor. Science 195: 181–183, 1977Google Scholar
  63. 63.
    Stricklin GP, Barter EA, Jeffrey JJ, Eisen AZ: Human skin collagenase: Isolation of precursor and active forms from both fibroblasts and organ cultures. Biochemistry 16: 1607–1615, 1977Google Scholar
  64. 64.
    Wahl LM, Wahl SM, Merganhagen SE, Martin GR: Collagenase production by endotoxin activated macrophages. Proc Natl Acad Sci 71: 3598–3601, 1974Google Scholar
  65. 65.
    Werb Z, Burleigh MC: A specific collagenase from rabbit fibroblasts in monolayer culture. Biochem J 137: 373–385, 1974Google Scholar
  66. 66.
    Passwell JH, Dayer JM, Gass OK, Edelson PJ: Regulation by Fc fragments of the section of collagenase, PGE2 and lysozyme by mouse peritoneal macrophages. J Immunol 125: 910–913, 1980Google Scholar
  67. 67.
    Halme J, Tyree B, Jeffrey JJ: Collagenase production by primary cultures of rat uterine cells. Partial purification and characterization of the enzyme. Arch Biochem Biophys 199: 51–60, 1980Google Scholar
  68. 68.
    Moscatelli D, Jaffe E, Rifkin DB: Tetadecanoyl phorbol acetate stimulates latent collagenase production by cultured human endothelial cells. Cell 10: 343–351, 1980Google Scholar
  69. 69.
    Puzas JE, Brand JS: Parathyroid hormone stimulation of collagenase secretion by isolated bone cells. Endocrinology 104: 559–562, 1979Google Scholar
  70. 70.
    Ridge SC, Oronsky AL, Kerwan SS: Induction of the synthesis of latent collagenase in chrondrocytes by a factor synthesized by activated macrophages. Arthritis Rheum 23: 448–454, 1980Google Scholar
  71. 71.
    Montfort I, Perez-Tamayo R: The distribution of Collagenase in normal rat tissues. J Histochem Cytochem 23: 910–920, 1975Google Scholar
  72. 72.
    Caulfield JB, Wolkowicz P: Inducible collagenolytic activity in isolated, perfused rat hearts. Am J Pathol 131: 199–205, 1988Google Scholar
  73. 73.
    Chakraborty A, Eghbali M: Collagenase activity in the normal rat myocardium: An immunohistochemical method. Histochemistry 92: 391–396, 1989Google Scholar
  74. 74.
    Michel JB, Salzmann JL, Ossondo Nlom M, Bruneval P, Barres D, Camilleri JP: Morphometric analysis of collagen network and plasma perfused capillary bed in the myocardium of rats during evolution of cardiac hypertrophy. Basic Res Cardiol 81: 142–154, 1986Google Scholar
  75. 75.
    Thiedemann KU, Holubarsch C, Medugorac I, Jacob R: Connective tissue content and myocardial stiffness in pressure overload hypertrophy. A combined study of morphologic, morphometric, biochemical and mechanical parameters. Basic Res Cardiol 78: 140–155, 1983Google Scholar
  76. 76.
    Jalil JE, Doering CW, Janicki JS, Pick R, Clark WA, Weber KT: Structural vs contractile protein remodeling and myocardial stiffness in hypertrophied rat left ventricle. J Mol Cell Cardiol 20: 1179–1187, 1988Google Scholar
  77. 77.
    Narayan S, Janicki JS, Shroff SG, Pick R, Weber KT: Myocardial collagen and mechanics after preventing hypertrophy in hypertensive rats. Am J Hypertension 2: 675–682, 1989Google Scholar
  78. 78.
    Krayenbuehl HP, Hess OM, Monrad ES, Schneider J, Mall G, Turina M: Left ventricular myocardial structure in aortic valve disease before, intermediate, and late after aortic valve replacement. Circulation 79: 744–755, 1989Google Scholar
  79. 79.
    Hess OM, Schneider J, Koch R, Bamert C, Grimm J, Krayenbuehl HP: Diastolic function and myocardial structure in patients with myocardial hypertrophy. Special reference to normalized viscoelastic data. Circulation 63: 360–371, 1981Google Scholar
  80. 80.
    Caspari PG, Newcomb M, Gibson K, Harris P: Collagen in the normal and hypertrophied human ventricle. Cardiovasc Res 11: 554–558, 1977Google Scholar
  81. 81.
    Schwarz F, Flameng W, Schaper J, Hehrlein F: Correlation between myocardial structure and diastolic properties of the heart in chronic aortic valve disease: Effects of corrective surgery. Am J Cardiol 42: 895–903, 1978Google Scholar
  82. 82.
    Schaper J, Schaper W: Ultrastructural correlates of reduced cardiac function in human heart disease. Eur Heart J 4(Suppl A): 35–42, 1983Google Scholar
  83. 83.
    Oldershaw J, Brooksby IAB, Davies MJ, Coltart DJ, Jenkins BS, Webb-Peploe MM: Correlations of fibrosis in endomyocardial biopsies from patients with aortic valve disease. Br Heart J 44: 609–611, 1980Google Scholar
  84. 84.
    St. John Sutton MG, Lie JT, Anderson KR, O'Brien PC, Frye RL: Histopathological specificity of hypertrophic obstructive cardiomyopathy. Br Heart J 44: 433–443, 1980Google Scholar
  85. 85.
    Naeye RL, Liedtke AJ: Consequences of intramyocardial arterial lesions in aortic valvular stenosis. Am J Pathol 85: 569–580, 1976Google Scholar
  86. 86.
    Pearlman ES, Weber KT, Janicki JS, Pietra G, Fishman AP: Muscle fiber orientation and connective tissue content in the hypertrophied human heart. Lab Invest 46: 158–164, 1982Google Scholar
  87. 87.
    Sen S, Bumpus FM: Collagen synthesis in development and reversal of cardiac hypertrophy in spontaneously hypertensive rats. Am J Cardiol 44: 954–958, 1979Google Scholar
  88. 88.
    Sen S, Tarazi RC, Bumpus FM: Effect of converting enzyme inhibitor (SQ14,225) on myocardial hypertrophy in spontaneously hypertensive rats. Hypertension 2: 169–176, 1980Google Scholar
  89. 89.
    Sen S, Tarazi RC, Bumpus FM: Reversal of cardiac hypertrophy in renal hypertensive rats: Medical vs. surgical therapy. Am J Physiol 240: H408-H42, 1981Google Scholar
  90. 90.
    Ruskoaho H: Regression of cardiac hypertrophy with drug treatment in spontaneously hypertensive rats. Med Biol 62: 263–276, 1984Google Scholar
  91. 91.
    Michel JB, Salzmann JL, De Lourdes Cerol M, Dussaule JC, Azizi M, Corman B, Camilleri JP, Corvol P: Myocardial effect of converting enzyme inhibition in hypertensive and normotensive rats. Am J Med 84(Suppl 3A): 12–21, 1988Google Scholar
  92. 92.
    Cutilletta AF, Dowell RT, Rudnik M, Arcilla RA, Zak R: Regression of myocardial hypertrophy: experimental model, changes in heart weight, nucleic acids and collagen. J Mol Cell Cardiol 7: 767–781, 1975Google Scholar
  93. 93.
    Cooper G, Marino TA: Complete reversibility of rat right ventricular chronic progressive pressure overload. Circ Res 54:323–331, 1984Google Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • Mahboubeh Eghbali
    • 1
  • Karl T. Weber
    • 1
  1. 1.Cardiovascular Institute, Michael Reese HospitalUniversity of Chicago Pritzker School of MedicineChicagoUSA

Personalised recommendations