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Extracellular Matrix and Cardiac Remodeling

  • Chapter
Interstitial Fibrosis in Heart Failure

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 253))

Conclusions

There is considerable evidence indicating that excessive ECCM can impair myocardial function in several cardiac diseases, so that antifibrotic agents might be beneficial in those conditions. Long-term inhibition of P4H or suppression of and TGF-β 1 represent two potential targets for decreasing ECCM and fibrosis in diseased myocardium. The ECCM also plays a major role in healing and remodeling after MI [4-7, 88, 118], which remains the leading cause of death and disability. After MI, however, the situation is complicated by the presence of an IZ and a NIZ (Figure 1), and the fact that ECCM disruption and damage during IZ healing, NIZ hypertrophy and interstitial fibrosis, and dilation involving both the IZ and NIZ all contribute to adverse LV structural remodeling. The sequence of MI, LV dysfunction, and progressive LV dilation underscores the fact that bad remodeling outweighs the good, and ECCM damage plays a pivotal role in this cycle. A major goal of therapy after MI is to prevent, control, and reverse all bad remodeling. One approach is to find adjunctive therapies that might protect the ECCM. MMPs can now be targeted with genetic approaches [198, 199]. Local gene therapy, applied to specific areas of the heart and IZ or NIZ regions might provide a safe and effective method for regional control of cardiac fibrosis.

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References

  1. Weber, K.T., et al., Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium. Circ Res, 1988. 62: p. 757–65.

    PubMed  CAS  Google Scholar 

  2. Weber, K.T., Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol, 1989. 13: p. 1637–52.

    Article  PubMed  CAS  Google Scholar 

  3. Weber, K.T., et al., Fibrillar collagen and remodeling of dilated canine left ventricle. Circulation, 1990. 82: p. 1387–401.

    PubMed  CAS  ISI  Google Scholar 

  4. Weber, K.T., Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. Circulation, 1997. 96: p. 4065–82.

    PubMed  CAS  ISI  Google Scholar 

  5. Jugdutt, B.I., Prevention of ventricular remodelling post myocardial infarction: timing and duration of therapy. Can J Cardiol, 1993. 9: p. 103–14.

    PubMed  CAS  Google Scholar 

  6. Jugdutt, B., Modification of left ventricular remodeling after myocardial infarction. In: The Failing Heart., Dhalla, N.S., et al., eds. Philadelphia, PA: The Lippincott-Raven Publishers, 1995: p. 231–245.

    Google Scholar 

  7. Jugdutt, B., Prevention of ventricular remodeling after myocardial infarction and in congestive heart failure. Heart Failure Reviews, 1996. 1: p. 115–129.

    Article  Google Scholar 

  8. Miller, E., Gay, S., Collagen structure and function. In: Wound Healing. Biochemical and clinical aspects, Cohen, I.K., et al., eds. Philadelphia, PA: WB Saunders Co., 1992: p. 130–151.

    Google Scholar 

  9. Alberts, B., et al., Molecular biology of the cell. Garland Publishing Co., 1994.

    Google Scholar 

  10. Olivetti, G., P. Anversa, and A.V. Loud, Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. II. Tissue composition, capillary growth, and sarcoplasmic alterations. Circ Res, 1980.46: p. 503–12.

    PubMed  CAS  Google Scholar 

  11. Zak, R., Development and proliferative capacity of cardiac muscle cells. Circ Res, 1974. 35: p. S17–26.

    Google Scholar 

  12. Eghbali, M., et al., Collagen chain mRNAs in isolated heart cells from young and adult rats. J Mol Cell Cardiol, 1988. 20: p. 267–76.

    Article  PubMed  CAS  Google Scholar 

  13. Eghbali, M., et al, Localization of types I, III and IV collagen mRNAs in rat heart cells by in situ hybridization. J Mol Cell Cardiol, 1989. 21: p. 103–13.

    Article  PubMed  CAS  Google Scholar 

  14. Eghbali, M., et al., Cardiac fibroblasts are predisposed to convert into myocyte phenotype: specific effect of transforming growth factor beta. Proc Natl Acad Sci U S A, 1991.88: p. 795–9.

    Article  PubMed  CAS  Google Scholar 

  15. Cleutjens, J.P., The role of matrix metalloproteinases in heart disease. Cardiovasc Res, 1996. 32: p. 816–21.

    Article  PubMed  CAS  Google Scholar 

  16. Nag, A.C., Study of non-muscle cells of the adult mammalian heart: a fine structural analysis and distribution. Cytobios, 1980. 28: p. 41–61.

    PubMed  CAS  ISI  Google Scholar 

  17. Frank, J.S. and G.A. Langer, The myocardial interstitium: its structure and its role in ionic exchange. J Cell Biol, 1974. 60: p. 586–601.

    Article  PubMed  CAS  Google Scholar 

  18. Weinberg, E.O., et al., Angiotensin-converting enzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis. Circulation, 1994. 90: p. 1410–22.

    PubMed  CAS  ISI  Google Scholar 

  19. Caulfield, J.B. and T.K. Borg, The collagen network of the heart. Lab Invest, 1979.40: p. 364–72.

    PubMed  CAS  Google Scholar 

  20. Robinson, T.F., L. Cohen-Gould, and S.M. Factor, Skeletal framework of mammalian heart muscle. Arrangement of inter-and pericellular connective tissue structures. Lab Invest, 1983. 49: p. 482–98.

    PubMed  CAS  Google Scholar 

  21. Robinson, T.F., et al., Morphology, composition, and function of struts between cardiac myocytes of rat and hamster. Cell Tissue Res, 1987. 249: p. 247–55.

    Article  PubMed  CAS  Google Scholar 

  22. Burton, A., Relation of structure to function of the tissues of the wall of vessels. Physiol Rev, 1954. 34: p. 619–642.

    PubMed  CAS  Google Scholar 

  23. Murad, S., et al., Regulation of collagen synthesis by ascorbic acid. Proc Natl Acad Sci U S A, 1981.78: p. 2879–82.

    Article  PubMed  CAS  Google Scholar 

  24. Penttinen, R.P., S. Kobayashi, and P. Bornstein, Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc Natl Acad Sci U S A, 1988. 85: p. 1105–8.

    Article  PubMed  CAS  Google Scholar 

  25. Eghbali, M., Cellular origin and distribution of transforming growth factor-beta in the normal rat myocardium. Cell Tissue Res, 1989. 256: p, 553–8.

    Article  PubMed  CAS  Google Scholar 

  26. Grotendorst, G.R., H. Okochi, and N. Hayashi, A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene. Cell Growth Differ, 1996. 7: p. 469–80.

    PubMed  CAS  ISI  Google Scholar 

  27. Meldrum, D.R., Tumor necrosis factor in the heart. Am J Physiol, 1998. 274: p. R577–95.

    PubMed  CAS  Google Scholar 

  28. Oikarinen, A.I. et al., Modulation of collagen metabolism by glucocorticoids. Receptor-mediated effects of dexamethasone on collagen biosynthesis in chick embryo fibroblasts and chondrocytes. Biochem Pharmacol, 1988. 37: p. 1451–62.

    Article  PubMed  CAS  Google Scholar 

  29. Nwogu, J.I., et al., Inhibition of collagen synthesis with prolyl 4-hydroxylase inhibitor improves left ventricular function and alters the pattern of left ventricular dilatation after myocardial infarction. Circulation, 2001. 104: p. 2216–21.

    Article  PubMed  CAS  ISI  Google Scholar 

  30. Brodsky, B. and N.K. Shah, Protein motifs. 8. The triple-helix motif in proteins. FASEB J, 1995. 9: p. 1537–46.

    PubMed  CAS  ISI  Google Scholar 

  31. Tyagi, S.C., Proteinases and myocardial extracellular matrix turnover. Mol Cell Biochem, 1997. 168: p. 1–12.

    Article  PubMed  CAS  Google Scholar 

  32. Woessner, JF. Jr., The matrix metalloproteinase family. In Matrix Metalloproteinases. Parks, W. and Mecham, R., eds. San Diego.CA: Academic Press, 1998: p. 1–14.

    Google Scholar 

  33. Jeffrey, J., Collagen Degradation. In Wound Healing. Biochemical and clinical aspects 1992: p. 177–194.

    Google Scholar 

  34. Tyagi, S.C., et al., Co-expression of tissue inhibitor and matrix metalloproteinase in myocardium. J Mol Cell Cardiol, 1995. 27: p. 2177–89.

    Article  PubMed  CAS  Google Scholar 

  35. Montfort, I. and R. Perez-Tamayo, The distribution of collagenase in normal rat tissues. J Histochem Cytochem, 1975. 23: p. 910–20.

    PubMed  CAS  Google Scholar 

  36. Spinale, F.G., et al., Matrix metalloproteinase inhibition during the development of congestive heart failure: effects on left ventricular dimensions and function. Circ Res, 1999. 85: p. 364–76.

    PubMed  CAS  Google Scholar 

  37. Rohde, L.E., et al., Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation, 1999. 99: p. 3063–70.

    PubMed  CAS  ISI  Google Scholar 

  38. Heymans, S., et al., Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med, 1999. 5: p. 1135–42.

    Article  PubMed  CAS  Google Scholar 

  39. Roten, L., et al., Effects of gene deletion of the tissue inhibitor of the matrix metalloproteinase-type 1 (TIMP-1) on left ventricular geometry and function in mice. J Mol Cell Cardiol, 2000. 32: p. 109–20.

    Article  PubMed  CAS  Google Scholar 

  40. Nagatomo, Y., et al., Differential effects of pressure or volume overload on myocardial MMP levels and inhibitory control. Am J Physiol, 2000. 278: p. H151–61.

    CAS  Google Scholar 

  41. Ducharme, A., et al., Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest, 2000. 106: p. 55–62.

    Article  PubMed  CAS  Google Scholar 

  42. Gunja-Smith, Z., et al., Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline cross-links. Am J Pathol, 1996. 148: p. 1639–48.

    PubMed  CAS  Google Scholar 

  43. Li, Y.Y., et al., Differential expression of tissue inhibitors of metalloproteinases in the failing human heart. Circulation, 1998. 98: p. 1728–34.

    PubMed  CAS  ISI  Google Scholar 

  44. Thomas, C.V., et al., Increased matrix metalloproteinase activity and selective upregulation in LV myocardium from patients with end-stage dilated cardiomyopathy. Circulation, 1998. 97: p. 1708–15.

    PubMed  CAS  ISI  Google Scholar 

  45. Spinale, F.G., et al., A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation, 2000. 102: p. 1944–9.

    PubMed  CAS  ISI  Google Scholar 

  46. Bonnin, C.M., M.P. Sparrow, and R.R. Taylor, Collagen synthesis and content in right ventricular hypertrophy in the dog. Am J Physiol, 1981. 241: p. H708–13.

    PubMed  CAS  Google Scholar 

  47. Brilla, C.G., J.S. Janicki, and K.T. Weber, Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy. Circulation, 1991. 83: p. 1771–9.

    PubMed  CAS  ISI  Google Scholar 

  48. Brilla, C.G., J.S. Janicki, and K.T. Weber, Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries. Circ Res, 1991. 69: p. 107–15.

    PubMed  CAS  Google Scholar 

  49. Brilla, C.G., L, Matsubara, and K.T. Weber, Advanced hypertensive heart disease in spontaneously hypertensive rats. Lisinopril-mediated regression of myocardial fibrosis. Hypertension, 1996. 28: p. 269–75.

    PubMed  CAS  ISI  Google Scholar 

  50. Mukherjee, D. and S. Sen, Collagen phenotypes during development and regression of myocardial hypertrophy in spontaneously hypertensive rats. Circ Res, 1990. 67: p. 1474–80.

    PubMed  CAS  Google Scholar 

  51. Oldershaw, P.J., et al., Correlations of fibrosis in endomyocardial biopsies from patients with aortic valve disease. Br Heart J, 1980. 44: p. 609–11.

    Article  PubMed  CAS  Google Scholar 

  52. Turto, H., Collagen metabolism in experimental cardiac hypertrophy in the rat and the effect of digitoxin treatment. Cardiovasc Res, 1977. 11: p. 358–66.

    Article  PubMed  CAS  Google Scholar 

  53. Skosey, J.L., et al., Biochemical correlates of cardiac hypertrophy. V. Labeling of collagen, myosin, and nuclear DNA during experimental myocardial hypertrophy in the rat. Circ Res, 1972. 31: p. 145–57.

    PubMed  CAS  Google Scholar 

  54. Jalil, J.E., et al., Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle. Circ Res, 1989. 64: p. 1041–50.

    PubMed  CAS  Google Scholar 

  55. Iimoto, D.S., J. W. Covell, and E. Harper, Increase in cross-linking of type I and type III collagens associated with volume-overload hypertrophy. Circ Res, 1988. 63: p. 399–408.

    PubMed  CAS  Google Scholar 

  56. Covell, J.W., Factors influencing diastolic function. Possible role of the extracellular matrix. Circulation, 1990. 81: p. III155–8.

    PubMed  CAS  Google Scholar 

  57. Douglas, P.S. and B. Tallant, Hypertrophy, fibrosis and diastolic dysfunction in early canine experimental hypertension. J Am Coll Cardiol, 1991. 17: p. 530–6.

    Article  PubMed  CAS  Google Scholar 

  58. van Krimpen, C., et al., Angiotensin I converting enzyme inhibitors and cardiac remodeling. Basic Res Cardiol, 1991. 86: p. 149–55.

    PubMed  Google Scholar 

  59. Jugdutt, B.I., M.J. Joljart, and M.I. Khan, Rate of collagen deposition during healing and ventricular remodeling after myocardial infarction in rat and dog models. Circulation, 1996. 94: p. 94–101.

    PubMed  CAS  ISI  Google Scholar 

  60. Pfeffer, M.A. and E. Braunwald, Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation, 1990. 81: p. 1161–72.

    PubMed  CAS  ISI  Google Scholar 

  61. Anversa, P., G. Olivetti, and J.M. Capasso, Cellular basis of ventricular remodeling after myocardial infarction. Am J Cardiol, 1991. 68: p. 7D–16D.

    Article  PubMed  CAS  Google Scholar 

  62. Pfeffer, J.M., et al., Progressive ventricular remodeling in rat with myocardial infarction. Am J Physiol, 1991. 260: p. H1406–14.

    PubMed  CAS  Google Scholar 

  63. Marijianowski, M.M., et al., Dilated cardiomyopathy is associated with an increase in the type I/type III collagen ratio: a quantitative assessment. J Am Coll Cardiol, 1995. 25: p. 1263–72.

    Article  PubMed  CAS  Google Scholar 

  64. Balghith, M. and B.I. Jugdutt, Assessment of diastolic dysfunction after acute myocardial infarction using Doppler echocardiography. Can J Cardiol, 2002. 18: p. 69–77.

    PubMed  Google Scholar 

  65. Michorowski, B., P. Senaratne, and B. Jugdutt, Myocardial infarct expansion. Cardiovasc Rev & Rep, 1987. 8: p. 42–47.

    Google Scholar 

  66. Jugdutt, B.I., Identification of patients prone to infarct expansion by the degree of regional shape distortion on an early two-dimensional echocardiogram after myocardial infarction. Clin Cardiol, 1990. 13: p. 28–40.

    Article  PubMed  CAS  Google Scholar 

  67. Gerdes, A.M., et al., Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy. Circulation, 1992. 86: p. 426–30.

    PubMed  CAS  ISI  Google Scholar 

  68. Villarreal, F. and N. Kim, Modulation of cardiac fibroblast function by growth factors and mechanical stimuli. Cardiovasc Pathol, 1998. 7: p. 145–151.

    Article  CAS  Google Scholar 

  69. Judd, J.T. and B.C. Wexler, Prolyl hydroxylase and collagen metabolism after experimental mycardial infarction. Am J Physiol, 1975. 228: p. 212–6.

    PubMed  CAS  Google Scholar 

  70. Casscells, W., et al., Transforming growth factor-beta 1 in normal heart and in myocardial infarction. Ann N Y Acad Sci, 1990. 593: p. 148–60.

    Article  PubMed  CAS  Google Scholar 

  71. Murry, C.E., et al., Macrophages express osteopontin during repair of myocardial necrosis. Am J Pathol, 1994. 145: p. 1450–62.

    PubMed  CAS  Google Scholar 

  72. Ohnishi, H., et al., Increased expression of connective tissue growth factor in the infarct zone of experimentally induced myocardial infarction in rats. J Mol Cell Cardiol, 1998. 30: p. 2411–22.

    Article  PubMed  CAS  Google Scholar 

  73. Chen, M.M., et al., CTGF expression is induced by TGF-beta in cardiac fibroblasts and cardiac myocytes: a potential role in heart fibrosis. J Mol Cell Cardiol, 2000, 32: p. 1805–19.

    Article  PubMed  CAS  Google Scholar 

  74. Deswal, A., et al., Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation, 2001. 103: p. 2055–9.

    PubMed  CAS  ISI  Google Scholar 

  75. Deten, A., et al., Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats. J Mol Cell Cardiol, 2001.33: p. 1191–207.

    Article  PubMed  CAS  Google Scholar 

  76. Sekita, S., et al., Studies on collagen in the experimental myocardial infarction. Jpn Circ J, 1985. 49: p. 171–8.

    PubMed  CAS  Google Scholar 

  77. Zhao, M.J., et al., Profound structural alterations of the extracellular collagen matrix in postischemic dysfunctional (“stunned”) but viable myocardium. J Am Coll Cardiol, 1987. 10: p. 1322–34.

    Article  PubMed  CAS  Google Scholar 

  78. Factor, S.M., et al., Alterations of the myocardial skeletal framework in acute myocardial infarction with and without ventricular rupture. A preliminary report. Am J Cardiovasc Pathol, 1987. 1: p. 91–7.

    PubMed  CAS  Google Scholar 

  79. Weisman, H.F., et al., Cellular mechanisms of myocardial infarct expansion. Circulation, 1988. 78: p. 186–201.

    PubMed  CAS  ISI  Google Scholar 

  80. Caulfield, J. and P. Wolkowicz, A mechanism for cardiac dilatation. Heart Failure, 1990. 6: p. 138–150.

    Google Scholar 

  81. Olivetti, G., et al., Side-to-side slippage of myocytes participates in ventricular wall remodeling acutely after myocardial infarction in rats. Circ Res, 1990. 67: p. 23–34.

    PubMed  CAS  Google Scholar 

  82. Takahashi, S., A.C. Barry, and S.M. Factor, Collagen degradation in ischaemic rat hearts. Biochem J, 1990. 265: p. 233–41.

    PubMed  CAS  Google Scholar 

  83. Charney, R.H., et al., Collagen loss in the stunned myocardium. Circulation, 1992. 85 p. 1483–90.

    PubMed  CAS  ISI  Google Scholar 

  84. Cleutjens, J.P., et al., Regulation of collagen degradation in the rat myocardium after infarction. J Mol Cell Cardiol, 1995. 27: p. 1281–92.

    Article  PubMed  CAS  Google Scholar 

  85. Cleutjens, J.P., et al., Collagen remodeling after myocardial infarction in the rat heart. Am J Pathol, 1995. 147: p. 325–38.

    PubMed  CAS  Google Scholar 

  86. Uusimaa, P., et al., Collagen scar formation after acute myocardial infarction: relationships to infarct size, left ventricular function, and coronary artery patency. Circulation, 1997. 96: p. 2565–72.

    PubMed  CAS  ISI  Google Scholar 

  87. Etoh, T., et al., Myocardial and interstitial matrix metalloproteinase activity after acute myocardial infarction in pigs. Am J Physiol, 2001. 281: p. H987–94.

    CAS  Google Scholar 

  88. Jugdutt, B.I. and R.W. Amy, Healing after myocardial infarction in the dog: changes in infarct hydroxyproline and topography. J Am Coll Cardiol, 1986. 7: p. 91–102.

    Article  PubMed  CAS  Google Scholar 

  89. Jugdutt, B.I., Left ventricular rupture threshold during the healing phase after myocardial infarction in the dog. Can J Physiol Pharmacol, 1987. 65: p. 307–16.

    PubMed  CAS  Google Scholar 

  90. Jugdutt, B.I., Effect of nitroglycerin and ibuprofen on left ventricular topography and rupture threshold during healing after myocardial infarction in the dog. Can J Physiol Pharmacol, 1988. 66: p. 385–95.

    PubMed  CAS  Google Scholar 

  91. Jugdutt, B.I., et al., Functional impact of remodeling during healing after non-Q wave versus Q wave anterior myocardial infarction in the dog. J Am Coll Cardiol, 1992. 20: p. 722–31.

    Article  PubMed  CAS  Google Scholar 

  92. Jugdutt, B.I., et al., Effect of enalapril on ventricular remodeling and function during healing after anterior myocardial infarction in the dog. Circulation, 1995. 91: p. 802–12.

    PubMed  CAS  ISI  Google Scholar 

  93. Jugdutt, B.I., et al., Combined captopril and isosorbide dinitrate during healing after myocardial infarction. Effect on ventricular remodeling, function, mass and collagen. J Am Coll Cardiol, 1995. 25: p. 1089–96.

    Article  PubMed  CAS  Google Scholar 

  94. Jugdutt, B.I., Effect of captopril and enalapril on left ventricular geometry, function and collagen during healing after anterior and inferior myocardial infarction in a dog model. J Am Coll Cardiol, 1995. 25: p. 1718–25.

    Article  PubMed  CAS  Google Scholar 

  95. Jugdutt, B.I., A. Lucas, and M.I. Khan, Effect of angiotensin-converting enzyme inhibition on infarct collagen deposition and remodelling during healing after transmural canine myocardial infarction. Can J Cardiol, 1997. 13: p. 657–68.

    PubMed  CAS  Google Scholar 

  96. Bergman, I., Two improved ad simplified methods for the spectrophotometric determination of hydroxyproline. Anal Chem, 1963. 35: p. 1961–1965.

    Article  CAS  Google Scholar 

  97. Sato, S., et al., Connective tissue changes in early ischemia of porcine myocardium: an ultrastructural study. J Mol Cell Cardiol, 1983. 15: p. 261–75.

    Article  PubMed  CAS  Google Scholar 

  98. Cannon, R.O., 3rd, et al., Early degradation of collagen after acute myocardial infarction in the rat. Am J Cardiol, 1983. 52: p. 390–5.

    Article  PubMed  CAS  Google Scholar 

  99. Whittaker, P., D.R. Boughner, and R.A. Kloner, Role of collagen in acute myocardial infarct expansion. Circulation, 1991. 84: p. 2123–34.

    PubMed  CAS  ISI  Google Scholar 

  100. Lu, L., et al., Matrix metalloproteinases and collagen ultrastructure in moderate myocardial ischemia and reperfusion in vivo. Am J Physiol, 2000. 279: p. H601–9.

    CAS  Google Scholar 

  101. Mann, D.L. and F.G. Spinale, Activation of matrix metalloproteinases in the failing human heart: breaking the tie that binds. Circulation, 1998. 98: p. 1699–702.

    PubMed  CAS  ISI  Google Scholar 

  102. Cheung, P.Y., et al., Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. Circulation, 2000. 101: p. 1833–9.

    PubMed  CAS  ISI  Google Scholar 

  103. Li, Y. Y., et al., Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices. Circulation, 2001. 104: p. 1147–52.

    Article  PubMed  CAS  ISI  Google Scholar 

  104. Danielsen, C.C., H. Wiggers, and H.R. Andersen, Increased amounts of collagenase and gelatinase in porcine myocardium following ischemia and reperfusion. J Mol Cell Cardiol, 1998. 30: p. 1431–42.

    Article  PubMed  CAS  Google Scholar 

  105. Eaton, L.W., et al., Regional cardiac dilatation after acute myocardial infarction: recognition by two-dimensional echocardiography. N Engl J Med, 1979. 300: p. 57–62.

    Article  PubMed  CAS  Google Scholar 

  106. Erlebacher, J.A., et al., Early dilation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement. J Am Coll Cardiol, 1984. 4: p. 201–8.

    Article  PubMed  CAS  Google Scholar 

  107. van Krimpen, C., et al., DNA synthesis in the non-infarcted cardiac interstitium after left coronary artery ligation in the rat: effects of captopril. J Mol Cell Cardiol, 1991. 23: p. 1245–53.

    Article  PubMed  Google Scholar 

  108. Litwin, S.E., et al., Contractility and stiffness of noninfarcted myocardium after coronary ligation in rats. Effects of chronic angiotensin converting enzyme inhibition. Circulation, 1991. 83: p. 1028–37.

    PubMed  CAS  ISI  Google Scholar 

  109. Volders, P.G., et al., Interstitial collagen is increased in the non-infarcted human myocardium after myocardial infarction. J Mol Cell Cardiol, 1993. 25: p. 1317–23.

    Article  PubMed  CAS  Google Scholar 

  110. Mallory, G., P. White, and S.-S. J, The speed of healing of myocardial infarction: a study of the pathologic anatomy in 72 cases. Am Heart J, 1939. 18: p. 647–671.

    Article  Google Scholar 

  111. Fishbein, M.C., D. Maclean, and P.R. Maroko, The histopathologic evolution of myocardial infarction. Chest, 1978. 73: p. 843–9.

    Article  PubMed  CAS  ISI  Google Scholar 

  112. Boyle, M.P. and H.F. Weisman, Limitation of infarct expansion and ventricular remodeling by late reperfusion. Study of time course and mechanism in a rat model. Circulation, 1993. 88: p. 2872–83.

    PubMed  CAS  ISI  Google Scholar 

  113. Kim, C.B. and E. Braunwald, Potential benefits of late reperfusion of infarcted myocardium. The open artery hypothesis. Circulation, 1993. 88: p. 2426–36.

    PubMed  CAS  ISI  Google Scholar 

  114. Jugdutt, B.I., Effect of reperfusion on ventricular mass, topography, and function during healing of anterior infarction. Am J Physiol, 1997. 272: p. H1205–11.

    PubMed  CAS  Google Scholar 

  115. Vracko, R. and D. Thorning, Contractile cells in rat myocardial scar tissue. Lab Invest, 1991. 65: p. 214–27.

    PubMed  CAS  Google Scholar 

  116. Guarda, E., et al., Effects of endothelins on collagen turnover in cardiac fibroblasts. Cardiovasc Res, 1993. 27: p. 2130–4.

    Article  PubMed  CAS  Google Scholar 

  117. Villarreal, F.J., et al., Identification of functional angiotensin II receptors on rat cardiac fibroblasts. Circulation, 1993. 88: p. 2849–61.

    PubMed  CAS  ISI  Google Scholar 

  118. Sun, Y. and K.T. Weber, Infarct scar: a dynamic tissue. Cardiovasc Res, 2000. 46: p. 250–6.

    Article  PubMed  CAS  Google Scholar 

  119. Willems, I.E., et al., The alpha-smooth muscle actin-positive cells in healing human myocardial scars. Am J Pathol, 1994. 145: p. 868–75.

    PubMed  CAS  Google Scholar 

  120. Sun, Y., et al., Cardiac angiotensin converting enzyme and myocardial fibrosis in the rat. Cardiovasc Res, 1994. 28: p. 1423–32.

    Article  PubMed  CAS  Google Scholar 

  121. Campbell, S.E., J.S. Janicki, and K.T. Weber, Temporal differences in fibroblast proliferation and phenotype expression in response to chronic administration of angiotensin II or aldosterone. J Mol Cell Cardiol, 1995. 27: p. 1545–60.

    Article  PubMed  CAS  Google Scholar 

  122. Sun, Y. and K.T. Weber, Angiotensin converting enzyme and myofibroblasts during tissue repair in the rat heart. J Mol Cell Cardiol, 1996. 28: p. 851–8.

    Article  PubMed  CAS  Google Scholar 

  123. Whittaker, P., D.R. Boughner, and R.A. Kloner, Analysis of healing after myocardial infarction using polarized light microscopy. Am J Pathol, 1989. 134: p. 879–93.

    PubMed  CAS  Google Scholar 

  124. Sappino, A.P., W. Schurch, and G. Gabbiani, Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest, 1990. 63: p. 144–61.

    PubMed  CAS  Google Scholar 

  125. Skalli, O., et al., Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins. Lab Invest, 1989. 60: p. 275–85.

    PubMed  CAS  Google Scholar 

  126. Jugdutt, B.I. and J.W. Warnica, Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications. Effect of timing, dosage, and infarct location. Circulation, 1988. 78: p. 906–19.

    PubMed  CAS  ISI  Google Scholar 

  127. Jugdutt, B.I., Intravenous nitroglycerin unloading in acute myocardial infarction. Am J Cardiol, 1991. 68: p. 52D–63D.

    Article  PubMed  CAS  Google Scholar 

  128. Pfeffer, M.A., et al., Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med, 1988. 319: p. 80–6.

    Article  PubMed  CAS  Google Scholar 

  129. Sharpe, N., et al., Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet, 1988. 1: p. 255–9.

    Article  PubMed  CAS  ISI  Google Scholar 

  130. Jugdutt, B.I., B.L. Michorowski, and C.T. Kappagoda, Exercise training after anterior Q wave myocardial infarction: importance of regional left ventricular function and topography. J Am Coll Cardiol, 1988. 12: p. 362–72.

    Article  PubMed  CAS  Google Scholar 

  131. Jugdutt, B.I. and C.A. Basualdo, Myocardial infarct expansion during indomethacin or ibuprofen therapy for symptomatic post infarction pericarditis. Influence of other pharmacologic agents during early remodelling. Can J Cardiol, 1989. 5: p. 211–21.

    PubMed  CAS  Google Scholar 

  132. St John Sutton, M., et al., Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation, 1994. 89: p. 68–75.

    Google Scholar 

  133. Pfeffer, M.A., et al., Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med, 1992. 327: p. 669–77.

    Article  PubMed  CAS  Google Scholar 

  134. Gaudron, P., et al., Progressive left ventricular dysfunction and remodeling after myocardial infarction. Potential mechanisms and early predictors. Circulation, 1993. 87: p. 755–63.

    PubMed  CAS  ISI  Google Scholar 

  135. Pfeffer, M.A., et al., Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction. The healing and early afterload reducing therapy trial. Circulation, 1997. 95: p. 2643–51.

    PubMed  CAS  ISI  Google Scholar 

  136. Jugdutt, B.I., B.L. Schwarz-Michorowski, and M.I. Khan, Effect of long-term captopril therapy on left ventricular remodeling and function during healing of canine myocardial infarction. J Am Coll Cardiol, 1992. 19: p. 713–21.

    Article  PubMed  CAS  Google Scholar 

  137. Jugdutt, B.I. and M.I. Khan, Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction. Circulation, 1994. 89: p. 2297–307.

    PubMed  CAS  ISI  Google Scholar 

  138. Jugdutt, B.I., et al., Impact of left ventricular unloading after late reperfusion of canine anterior myocardial infarction on remodeling and function using isosorbide-5-mononitrate. Circulation, 1995. 92: p. 926–34.

    PubMed  CAS  ISI  Google Scholar 

  139. Jugdutt, B.I., et al., Effect of prolonged inotropic stimulation on ventricular remodeling during healing after myocardial infarction in the dog: mechanistic insights. J Am Coll Cardiol, 1996. 27: p. 1787–95.

    Article  PubMed  CAS  Google Scholar 

  140. Jugdutt, B.I. and S. Musat-Marcu, Opposite effects of amlodipine and enalapril on infarct collagen and remodelling during healing after reperfused myocardial infarction. Can J Cardiol, 2000. 16: p. 617–25.

    PubMed  CAS  Google Scholar 

  141. Jugdutt, B.I., et al., Vascular remodeling during healing after myocardial infarction in the dog model: effects of reperfusion, amlodipine and enalapril. J Am Coll Cardiol, 2002. 39: p. 1538–45.

    Article  PubMed  Google Scholar 

  142. Jugdutt, B.I., Delayed effects of early infarct-limiting therapies on healing after myocardial infarction. Circulation, 1985. 72: p. 907–14.

    PubMed  CAS  ISI  Google Scholar 

  143. Jugdutt, B.I., Myocardial salvage by intravenous nitroglycerin in conscious dogs: loss of beneficial effect with marked nitroglycerin-induced hypotension. Circulation, 1983. 68: p. 673–84.

    PubMed  CAS  ISI  Google Scholar 

  144. Group, C.T.S., Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival study. N Engl J Med, 1987. 316: p. 1429–1435.

    Google Scholar 

  145. Pouleur, H., et al., Effects of long-term enalapril therapy on left ventricular diastolic properties in patients with depressed ejection fraction. SOLVD Investigators. Circulation, 1993. 88: p. 481–91.

    PubMed  CAS  ISI  Google Scholar 

  146. Pfeffer, J.M., M. A. Pfeffer, and E. Braunwald, Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res, 1985. 57: p. 84–95.

    PubMed  CAS  Google Scholar 

  147. Knowlton, A.A., et al., Rapid expression of fibronectin in the rabbit heart after myocardial infarction with and without reperfusion. J Clin Invest, 1992. 89: p. 1060–8.

    Article  PubMed  CAS  Google Scholar 

  148. Connelly, C.M., et al., Reversible and irreversible elongation of ischemic, infarcted, and healed myocardium in response to increases in preload and afterload. Circulation, 1991. 84: p. 387–99.

    PubMed  CAS  ISI  Google Scholar 

  149. McCormick, R.J., et al., Regional differences in LV collagen accumulation and mature cross-linking after myocardial infarction in rats. Am J Physiol, 1994. 266: p. H354–9.

    PubMed  CAS  Google Scholar 

  150. Honan, M.B., et al., Cardiac rupture, mortality and the timing of thrombolytic therapy: a meta-analysis. J Am Coll Cardiol, 1990. 16: p. 359–67.

    Article  PubMed  CAS  Google Scholar 

  151. Beltrami, C.A., et al., Structural basis of end-stage failure in ischemic cardiomyopathy in humans. Circulation, 1994. 89: p. 151–63.

    PubMed  CAS  ISI  Google Scholar 

  152. Schaper, J. and B. Speiser, The extracellular matrix in the failing human heart. Basic Res Cardiol, 1992. 87: p. 303–9.

    Article  PubMed  Google Scholar 

  153. Mukherjee, D. and S. Sen, Alteration of collagen phenotypes in ischemic cardiomyopathy. J Clin Invest, 1991. 88: p. 1141–6.

    Article  PubMed  CAS  Google Scholar 

  154. Capasso, J.M., T.F. Robinson, and P. Anversa, Alterations in collagen cross-linking impair myocardial contractility in the mouse heart. Circ Res, 1989. 65: p. 1657–64.

    PubMed  CAS  Google Scholar 

  155. Woodiwiss, A.J., et al., Reduction in myocardial collagen cross-linking parallels left ventricular dilatation in rat models of systolic chamber dysfunction. Circulation, 2001. 103: p. 155–60.

    PubMed  CAS  ISI  Google Scholar 

  156. Hort, W., Untersuchungen zur funktionellen Morphologie des Bindegewebsgerustes und der Blutgefasse der linken Herzkammerwand. Virchows Arch Path Anat, 1960.333: p. 565–581.

    Article  CAS  Google Scholar 

  157. Holmgren, E., Ueber die trophospongien der quergestreiften muskelfasern, nebst bemerkungen uber den allgemeinen bau dieser fasern. Arch Mikrosk Anat, 1907. 71: p. 165–174.

    Article  Google Scholar 

  158. Nagle, E., Die mechanischen Eigenschaften von Perimysium internum und Sarkolemm bei den quergestreiften Muskelfasern. Z Zellforsch Mikrosk Anat, 1935. 22: p. 694–706.

    Article  Google Scholar 

  159. Wickline, S.A., et al., Structural remodeling of human myocardial tissue after infarction. Quantification with ultrasonic backscatter. Circulation, 1992. 85: p. 259–68.

    PubMed  CAS  ISI  Google Scholar 

  160. Gupta, K.B., et al., Changes in passive mechanical stiffness of myocardial tissue with aneurysm formation. Circulation, 1994. 89(5): p. 2315–26.

    PubMed  CAS  ISI  Google Scholar 

  161. Holmes, J.W., et al., Scar remodeling and transmural deformation after infarction in the pig. Circulation, 1994. 90: p. 411–20.

    PubMed  CAS  ISI  Google Scholar 

  162. Linzbach, A., Heart failure from the point of view of quantitative anatomy. Am J Cardiol, 1960. 5: p. 370–382.

    Article  PubMed  CAS  Google Scholar 

  163. Caulfield, J.B. and P. Wolkowicz, Inducible collagenolytic activity in isolated perfused rat hearts. Am J Pathol, 1988. 131: p. 199–205.

    PubMed  CAS  Google Scholar 

  164. MacKenna, D.A., et al., Contribution of collagen matrix to passive left ventricular mechanics in isolated rat hearts. Am J Physiol, 1994. 266: p. H1007–18.

    PubMed  CAS  Google Scholar 

  165. Bing, O.K., et al., The effect of lathyrogen beta-amino proprionitrile (BAPN) on the mechanical properties of experimentally hypertrophied rat cardiac muscle. Circ Res, 1978. 43: p. 632–7.

    PubMed  CAS  Google Scholar 

  166. Sato, Y., et al., Measuring serum aminoterminal type III procollagen peptide, 7S domain of type IV collagen, and cardiac troponin T in patients with idiopathic dilated cardiomyopathy and secondary cardiomyopathy. Heart, 1997. 78: p. 505–8.

    PubMed  CAS  ISI  Google Scholar 

  167. Host, N.B., et al., The aminoterminal propeptide of type III procollagen provides new information on prognosis after acute myocardial infarction. Am J Cardiol, 1995. 76: p. 869–73.

    Article  PubMed  CAS  Google Scholar 

  168. Klappacher, G., et al., Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis. Am J Cardiol, 1995. 75: p. 913–8.

    Article  PubMed  CAS  Google Scholar 

  169. Zannad, F., et al., Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation, 2000. 102: p. 2700–6.

    PubMed  CAS  ISI  Google Scholar 

  170. Latini, R., et al., ACE inhibitor use in patients with myocardial infarction. Summary of evidence from clinical trials. Circulation, 1995. 92: p. 3132–7.

    PubMed  CAS  ISI  Google Scholar 

  171. Cohn, J.N., R. Ferrari, and N. Sharpe, Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol, 2000. 35: p. 569–82.

    Article  PubMed  CAS  Google Scholar 

  172. Matsubara, H., Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. Circ Res, 1998. 83: p. 1182–91.

    PubMed  CAS  Google Scholar 

  173. Nio, Y., et al., Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. J Clin Invest, 1995. 95: p. 46–54.

    Article  PubMed  CAS  Google Scholar 

  174. Brilla, C.G., et al., Collagen metabolism in cultured adult rat cardiac fibroblasts: response to angiotensin II and aldosterone. J Mol Cell Cardiol, 1994. 26: p. 809–20.

    Article  PubMed  CAS  Google Scholar 

  175. Urata, H., et al., Angiotensin II-forming pathways in normal and failing human hearts. Circ Res, 1990. 66: p. 883–90.

    PubMed  CAS  Google Scholar 

  176. Jugdutt, B., M. Crawford, and W.C. Saunders, Angiotensin II receptor blockers. Cardiology Clinics Annual of Drug Therapy, 1998. 2: p. 1–17.

    Google Scholar 

  177. Jugdutt, B. and A. Kimchi, New advances in the use of ATI receptor blockers (ARBs). In, Proceedings of the 2nd International Congress on Heart Disease-New trends in Research, Diagnosis and Treatment. Medimond Medical Publications, 2001: p. 531–538.

    Google Scholar 

  178. Rousseau, M.F., et al., Progression of left ventricular dysfunction secondary to coronary artery disease, sustained neurohormonal activation and effects of ibopamine therapy during long-term therapy with angiotensin-converting enzyme inhibitor. Am J Cardiol, 1994. 73: p. 488–93.

    Article  PubMed  CAS  Google Scholar 

  179. Baruch, L., et al., Augmented short-and long-term hemodynamic and hormonal effects of an angiotensin receptor blocker added to angiotensin converting enzyme inhibitor therapy in patients with heart failure. Vasodilator Heart Failure Trial (V-HeFT) Study Group. Circulation, 1999. 99: p. 2658–64.

    PubMed  CAS  ISI  Google Scholar 

  180. Sen, S. and F.M. Bumpus, Collagen synthesis in development and reversal of cardiac hypertrophy in spontaneously hypertensive rats. Am J Cardiol, 1979. 44(5): p. 954–8.

    Article  PubMed  CAS  Google Scholar 

  181. Tyagi, S.C., A. Ratajska, and K.T. Weber, Myocardial matrix metalloproteinase(s): localization and activation. Mol Cell Biochem, 1993. 126: p. 49–59.

    Article  PubMed  CAS  Google Scholar 

  182. Keeley, F. W., A. Elmoselhi, and F.H. Leenen, Enalapril suppresses normal accumulation of elastin and collagen in cardiovascular tissues of growing rats. Am J Physiol, 1992. 262: p. H1013–21.

    PubMed  CAS  Google Scholar 

  183. Michel, J.B., et al., Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction. Circ Res, 1988. 62: p. 641–50.

    PubMed  CAS  Google Scholar 

  184. Rousseau, M.F., et al., Effects of benazeprilat on left ventricular systolic and diastolic function and neurohumoral status in patients with ischemic heart disease. Circulation, 1990. 81: p. III 123-9.

    Google Scholar 

  185. Smits, J.F., et al., Angiotensin II receptor blockade after myocardial infarction in rats: effects on hemodynamics, myocardial DNA synthesis, and interstitial collagen content. J Cardiovasc Pharmacol, 1992. 20: p. 772–8.

    PubMed  CAS  Google Scholar 

  186. Ertl, G. and B. Jugdutt, ACE inhibition after myocardial infarction: can megatrials provide answers? Lancet, 1994. 344: p. 1068–9.

    Article  PubMed  CAS  ISI  Google Scholar 

  187. Nguyen, Q.T., et al., Endothelin A receptor blockade causes adverse left ventricular remodeling but improves pulmonary artery pressure after infarction in the rat. Circulation, 1998. 98: p. 2323–30.

    PubMed  CAS  ISI  Google Scholar 

  188. Caspari, P.G., K. Gibson, and P. Harris, Changes in myocardial collagen in normal development and after beta blockade. Recent Adv Stud Cardiac Struct Metab, 1975. 7: p. 99–104.

    PubMed  CAS  Google Scholar 

  189. Gudbjarnason, S., et al, Stimulation of reparative processes following experimental myocardial infarction. Arch Intern Med, 1966. 118: p. 33–40.

    Article  PubMed  CAS  Google Scholar 

  190. Castagnino, H.E., et al., Preservation of the myocardial collagen framework by human growth hormone in experimental infarctions and reduction in the incidence of ventricular aneurysms. Int J Cardiol, 1992. 35: p. 101–14.

    Article  PubMed  CAS  Google Scholar 

  191. Scott-Burden, T., et al., Platelet-derived growth factor suppresses and fibroblast growth factor enhances cytokine-induced production of nitric oxide by cultured smooth muscle cells. Effects on cell proliferation. Circ Res, 1992. 71: p. 1088–100.

    PubMed  CAS  Google Scholar 

  192. Ju, H., et al., Effect of AT1 receptor blockade on cardiac collagen remodeling after myocardial infarction. Cardiovasc Res, 1997. 35: p. 223–32.

    Article  PubMed  CAS  Google Scholar 

  193. Jordan, J.E., Z.Q. Zhao, and J. Vinten-Johansen, The role of neutrophils in myocardial ischemia-reperfusion injury. Cardiovasc Res, 1999. 43: p. 860–78.

    Article  PubMed  CAS  Google Scholar 

  194. Group, L.S., Late Assessment of Thrombolytic Efficacy (Late) study with alteplase 6024 hours after onset of acute myocardial infarction. Lancet, 1993. 25; 342: p. 759–766.

    Google Scholar 

  195. Morita, M., et al., Effects of late reperfusion on infarct expansion and infarct healing in conscious rats. Am J Pathol, 1993. 143: p. 419–30.

    PubMed  CAS  Google Scholar 

  196. Przyklenk, K. and R.A. Kloner, Superoxide dismutase plus catalase improve contractile function in the canine model of the “stunned myocardium”. Circ Res, 1986. 58: p. 148–56.

    PubMed  CAS  Google Scholar 

  197. Peuhkurinen, K.J., et al., Thrombolytic therapy with streptokinase stimulates collagen breakdown. Circulation, 1991. 83: p. 1969–75.

    PubMed  CAS  ISI  Google Scholar 

  198. Pyo, R., et al., Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest, 2000. 105: p. 1641–9.

    Article  PubMed  CAS  Google Scholar 

  199. Bigatel, D.A., et al., The matrix metalloproteinase inhibitor BB-94 limits expansion of experimental abdominal aortic aneurysms. J Vase Surg, 1999. 29: p. 130–8.

    Article  CAS  Google Scholar 

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  1. Cardiology Division of the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

    Bodh I. Jugdutt

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  1. Department of Medicine, University of California, San Diego School of Medicine, San Diego, California, USA

    Francisco J. Villarreal M.D., Ph.D.

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Jugdutt, B.I. (2005). Extracellular Matrix and Cardiac Remodeling. In: Villarreal, F.J. (eds) Interstitial Fibrosis in Heart Failure. Developments in Cardiovascular Medicine, vol 253. Springer, New York, NY. https://doi.org/10.1007/0-387-22825-X_2

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