Skip to main content

Advertisement

SpringerLink
Log in

Extracellular matrix proteins and matrix metalloproteinases differ between various right and left ventricular sites in end-stage cardiomyopathies

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

This study was undertaken to investigate whether there might be differences in the distribution of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), depending on their specific sites within the heart. We investigated 33 explanted human hearts, 15 with dilated cardiomyopathy (DCM) and 18 with ischemic cardiomyopathy (ICM). Transmural samples from the right ventricle, the interventricular septum and the left ventricle, either from near the apex or from near the base were taken from every heart. Frozen sections were processed for connective tissue staining and immunohistochemistry for collagens type I, III, IV, laminin and fibronectin, as well as MMP-1, -2 and -9. Volume densities of laminin in ICM as well as of fibronectin and collagen types I and IV in DCM showed significant differences between right and left ventricular sites. The volume densities of matrix proteins usually did not reveal significant differences among the three left ventricular sites tested in both DCM and ICM. MMPs partly showed differences between the right and the left ventricular myocardium. These results suggest that the distributions of ECM proteins and MMPs differ between the two ventricles in both end-stage DCM and ICM. This gives rise to the hypothesis that a specific pattern of ECM degradation exists in the right and left ventricular myocardium.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1 A
Fig. 2 A
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Adler CP, Neuburger M, Herget GW, Mühlbach D (1997) Regeneration processes in human myocardium after acute ischaemia-quantitative determination of DNA, cell number and collagen content. Virchows Arch 430:149–153

    Google Scholar 

  2. Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E, Quaini F, Sonnenblick EH, Olivetti G, Anversa P (1994) Myocardial function/valvular heart disease/hypertensive heart disease: structural basis of end-stage failure in ischemic cardiomyopathy in humans. Circulation 89:151–163

    Google Scholar 

  3. Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E, Sonnenblick EH, Olivetti G, Anversa P (1995) The cellular basis of dilated cardiomyopathy in humans. J Mol Cell Cardiol 27:291–305

    Google Scholar 

  4. Birkdal-Hansen H (1995) Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 7:728–735

    Article  CAS  PubMed  Google Scholar 

  5. Bosman FT, Stamenkovic I (2003) Functional structure and composition of the extracellular matrix. J Pathol 200:423–428

    Google Scholar 

  6. Coker ML, Doscher MA, Thomas ChV, Galis ZS, Spinale FG (1999) Matrix metalloproteinase synthesis and expression in isolated myocyte preparations. Am J Physiol Heart Circ Physiol 277:777–787

    Google Scholar 

  7. Coker ML, Zellner JL, Crumbley AJ, Spinale FG (1999) Defects in matrix metalloproteinase inhibitory stoichiometry and selective MMP induction in patients with nonischemic or ischemic dilated cardiomyopathy. Ann N Y Acad Sci 878:559–562

    Google Scholar 

  8. Corradi D, Callegari S, Benussi S, Nascimbene S, Pastori P, Calvi S, Maestri R, Astorri E, Pappone C, Alfieri O (2004) Regional left atrial interstitial remodeling in patients with chronic atrial fibrillation undergoing mitral-valve surgery. Virchows Archiv 445:498–505

    Google Scholar 

  9. Diez J (2002) Emerging role of matrix metalloproteinases in the pathophysiology of cardiac diseases. Eur J Clin Invest 32:291–294

    Google Scholar 

  10. Feldman AM, Li YY, McTiernan CF (2001) Matrix metalloproteinases in pathophysiology and treatment of heart failure. Lancet 357:654–655

    Google Scholar 

  11. Florholmen G, Andersson KB, Yndestad A, Austbø B, Henriksen UL, Christensen G (2004) Leukaemia inhibitory factor alters expression of genes involved in rat cardiomyocyte energy metabolism. Acta Physiol Scan 180:133–142

    Google Scholar 

  12. Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson WG, Quaranta V (1997) Induction of cell migration by matrix metalloproteinase-2 cleavage of laminin. Science 277:225–228

    Article  CAS  PubMed  Google Scholar 

  13. Gunderson HJG, Osterby R (1981) Optimizing sampling efficiency of stereological studies in biology or “Do more less well!” J Microscopy 121:65–73

    Google Scholar 

  14. Heeneman S, Cleutjens JP, Faber BC, Creemers EE, van Suylen RJ, Lutgens E, Cleutjens KB, Daemen MJ (2003) The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis. J Pathol 200:516–525

    Google Scholar 

  15. Ishikawa Y, Asuwa N, Ishii T, Ito K, Akasaka Y, Masuda T, Zhang L, Kiguchi H (2000) Collagen alteration in vascular remodeling by hemodynamic factors. Virchows Arch 437:138–148

    Google Scholar 

  16. Klappacher G, Franzen P, Haab D, Mehrabi M, Binder M, Plesch K, Pacher R, Grimm M, Pribill I, Eichler HG, Glogar HD (1995) Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis. Am J Cardiol 75:913–918

    Google Scholar 

  17. Li YY, Feldman AM, Sun Y, McTiernan CF (1998) Differential expression of tissue inhibitors of metalloproteinases in the failing human heart. Circulation 98:1728–1734

    Google Scholar 

  18. Li YY, McTiernan CF, Feldman AM (2000) Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovasc Res 46:214–224

    Google Scholar 

  19. Lu L, Gunja-Smith Z, Woessner JF, Ursell PC, Nissen T, Galardy RE, Xu Y, Zhu P, Schwartz GG (2000) Matrix metalloproteinases and collagen ultrastructure in moderate myocardial ischemia and reperfusion in vivo. Am J Physiol Heart Circ Physiol 279:601–609

    Google Scholar 

  20. Mundhenke M, Schwartzkopff B, Strauer B (1997) Structural analysis of arteriolar and myocardial remodelling in the subendocardial region of patients with hypertensive disease and hypertrophic cardiomyopathy. Virchows Arch 431:265–273

    Google Scholar 

  21. Nogami K, Kusachi S, Nunoyama H, Kondo J, Endo C, Yamamoto K, Murakami T, Tsuji T (1996) Extracellular matrix components in dilated cardiomyopathy. Jpn Heart J 37:483–494

    Google Scholar 

  22. Pauschinger M, Knopf D, Petschauer S, Doerner A, Poller W, Schwimmbeck PL, Kuhl U, Schultheiss HP (1999) Dilated cardiomyopathy is associated with significant changes in collagen type I/III ratio. Circulation 99:2750–2756

    Google Scholar 

  23. Pauschinger M, Chandrasekharan K, Li J, Schwimmbeck PL, Noutsias M, Schultheiss HP (2002) Remodeling der extrazellulären Matrix bei dilatativer Kardiomyopathie. Herz 27:677–682

    Google Scholar 

  24. Reinhardt D, Sigusch HH, Hensse J, Tyagi SC, Korfer R, Figulla HR (2002) Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP. Heart 88:525–530

    Google Scholar 

  25. Rossi MA (1991) Patterns of myocardial fibrosis in idiopathic cardiomyopathies and chronic Chagasic cardiopathy. Can J Cardiol 7:287–294

    Google Scholar 

  26. Rossi MA (1998) Pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans. J Hypertension 16:1031–1041

    Google Scholar 

  27. Rossi MA, Abreu MA, Santoro LS (1998) Connective tissue skeleton of the human heart. A deminstration by cell-maceration scanning electron microscope methode. Circulation 97:934–935

    Google Scholar 

  28. Sandmann S, Bohle RM, Dreyer T, Unger T (2000) The T-type calcium channel blocker mibefradil reduced interstitial and perivascular fibrosis and improved hemodynamic parameters in myocardial infarction-induced cardiac failure in rats. Virchows Arch 436:147–157

    Google Scholar 

  29. Schaper J, Speiser B (1992) The extracellular matrix in the failing human heart. Basic Res Cardiol 87[Suppl]:303–309

    Google Scholar 

  30. Soini Y, Satta J, Määttä M, Autio-Harmainen H (2001) Expression of MMP-2, MMP-9, MT1-MMP, TIMP-1and TIMP-2 mRNA in valvular lesions of the heart. J Pathol 194:225–231

    Google Scholar 

  31. Spinale FG (2002) Matrix metalloproteinases. Regulation and dysregulation in the failing heart. Circ Res 90:520–530

    CAS  PubMed  Google Scholar 

  32. Stamenkovic I (2003) Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 200:448–464

    Google Scholar 

  33. Tyagi SC (1997) Proteinases and myocardial extracellular matrix turnover. Moll Cell Biochem 168:1–12

    Google Scholar 

  34. Tyagi SC, Campbell SE, Reddy HK, Tjahja E, Voelker DJ (1996) Matrix metalloproteinase activity expression in infarcted, noninfarcted and dilated cardiomyopathic human hearts. Mol Cell Biochem 155:13–21

    Google Scholar 

  35. Unverferth DV, Baker PB, Swift SE, Chaffee R, Fetters JK, Uretsky BV, Thompson ME, Leier CV (1986) Extent of myocardial fibrosis and cellular hypertrophy in dilated cardiomyopathy. Am J Cardiol 57:816–820

    Google Scholar 

  36. Wang W, Schulze CJ, Suarez-Pinzon WL, Dyck JRB, Sawicki G, Schulz R (2002) Intracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion in injury. Circulation 106:1543–1549

    Google Scholar 

  37. Weibel ER (ed) (1979) Stereological methods, vol.1. Practical methods for biological morphometry, 1st edn. Academic Press, London, pp 101–161

Download references

Acknowledgements

This work was supported by the Forschungsfoerderungs-Programm of the University of Heidelberg, project-no. 150 /2001. The authors thank Ms. G. Gorsberg and Ms. B. Hofmann for their excellent technical assistance and Ms. U. Horr and Mr. J Moyers for their help with preparation of the photographs.

Author information

Authors and Affiliations

  1. Department of Pathology, University of Heidelberg, INF 220/1, 69120 , Heidelberg, Germany

    E. Herpel, S. Singer, C. Flechtenmacher, H. F. Otto & P. A. Schnabel

  2. Department of Medical Biometry, University of Heidelberg, Germany

    M. Pritsch

  3. Department of Cardiac Surgery, University of Heidelberg, Germany

    F.-U. Sack & S. Hagl

Authors
  1. E. Herpel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Flechtenmacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Pritsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F.-U. Sack
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Hagl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. A. Katus
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Haass
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H. F. Otto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P. A. Schnabel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. A. Schnabel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herpel, E., Singer, S., Flechtenmacher, C. et al. Extracellular matrix proteins and matrix metalloproteinases differ between various right and left ventricular sites in end-stage cardiomyopathies. Virchows Arch 446, 369–378 (2005). https://doi.org/10.1007/s00428-004-1177-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-004-1177-z

Keywords

Search

Navigation