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Expression of Cytoskeletal, Linkage and Extracellular Proteins in Failing Dog Myocardium

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Abstract

In the setting of chronic heart failure (HF), progressive left ventricular (LV) dysfunction and chamber remodeling may be due, in part, to altered expression and disorganization of cytoskeletal, linkage and extracellular proteins. This brief review describes changes in expression of cytoskeletal, linkage and extracellular protein using LV tissue obtained from dogs with progressive HF produced by multiple sequential intracoronary microembolizations. LV tissue samples from 6 untreated HF dogs (LV ejection fraction 20% to 25%) and 3 normal dogs were used. Sections from freshly frozen tissue were prepared, immunostained for specific proteins and studies by confocal microscopy. In failing hearts, confocal microscopy showed disorganization of key cytoskeletal proteins that, when combined with the loss of myofilaments and sarcomeric skeleton, suggest substantial cardiomyocyte remodeling. Cardiomyocytes in areas bordering old infarcts invariably exhibited disorganization of α-actinin. The cytoskeleton protein desmin showed increased expression in areas of extensive fibrosis. Staining for pancadherin showed interruptions of intercalated disks in areas of intensive interstitial fibrosis. Observation of increased fibronectin and increased interstitial cellularity based on vimentin labeling is suggestive of ongoing fibrosis. Based on these findings, we conclude that the structural changes observed in failing LV myocardium of dogs with intracoronary microembolizations-induced HF are extensive and typical of those seen and previously described in LV myocardium of explanted failed human hearts. The observed structural changes in this experimental model of HF also support the notion that these cytoskeletal, linkage and extracellular disorganization of structural proteins may be important maladaptations that contribute, albeit in part, to the progression of LV dysfunction and remodeling characteristic of the HF state.

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References

  1. Anversa P, Olivetti G, Capasso JM. Cellular basis of ventricular remodeling after myocardial infarction. Am J Cardiol 1991;68:7D–16D.

    Article  CAS  PubMed  Google Scholar 

  2. Sharov VG, Sabbah HN, Shimoyama H, Ali AS, Levine TB, Lesch M, Goldstein S. Abnormalities of contractile structures in viable myocytes of failing heart. Intl J Cardiol 1994;43:287–297.

    CAS  Google Scholar 

  3. Sabbah HN, Sharov VG, Riddle JM, Kono T, Leach M, Goldstein S. Mitochondrial abnormalities in myocardium of dogs with chronic heart failure. J Mol Call Cardiol 1992;24:1333–1347.

    CAS  Google Scholar 

  4. Schaper J, Hein S. The structural correlate of reduced cardiac function in human dilated cardiomyopathy. Heart Failure 1993;9:95–111.

    Google Scholar 

  5. Heling A, Zimmermann R, Kostin S, Maeno Y, Hein S, Devaux B, Baurer E, Klovekorn WP, Schlepper M, Schaper W, Schaper J. Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium. Circ Res 2000;86:846–853.

    CAS  PubMed  Google Scholar 

  6. Tsutsui H, Ishihara K, Cooper G. Cytoskeletal role for contractile dysfunction of hypertrophied myocardium. Science 1993;260:682–687.

    CAS  PubMed  Google Scholar 

  7. Tsutsui H, Tagawa H, Kent RL, McCollam PL, Ishihara K, Nagatsu M, Cooper G. Role of microtubules in contractile dysfunction of hypertrophied cardiocytes. Circulation 1994;90:533–555.

    CAS  PubMed  Google Scholar 

  8. Tagawa H, Koide M, Sato I, Cooper G. Cytoskeletal role in the contractile dysfunction of cardiomyocytes from hypertrophied and failing right ventricular myocardium. Proc Assoc Am Physicians 1996;108:218–229.

    CAS  PubMed  Google Scholar 

  9. Tagawa H, Rozich JD, Tsutsui H, Narishige T, Kuppuswamy D, Sato H, McDermott PJ, Koide M, Cooper G. Basis for increased microtubules in pressure-hypertrophied cardiocytes. Circulation 1996;93:1230–1243.

    CAS  PubMed  Google Scholar 

  10. Tagawa H, Wang N < Narishige T, Ingber DE, Zile MR, Cooper G. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy. Circ Res 1997;80:281–289.

    CAS  PubMed  Google Scholar 

  11. Sato II, Nagai T, Kuppuswamy D, Narishige T, Koide M, Menick DR, Cooper G. Microtubule stabilization in pressure overload cardiac hypertrophy. J Cell Biol 1997;139:963–973.

    Article  CAS  PubMed  Google Scholar 

  12. Watson PA, Hannan R, Carl LL, Giger KE. Contractile activity and passive strength regulate tubulin mRNA and protein content in cardiac myocytes. Am J Physiol 1966;271:C684–C689.

    Google Scholar 

  13. Sabbah HN, Stein PD, Kono T, Georghiade M, Levine TB, Jafri S, Hawkins ET, Goldstein S. A canine model of chronic heart failure produced by multiple sequential coronary microembolizations. Am J Physiol 1991;260:H13479– H1384.

    Google Scholar 

  14. Devaux B, Scholz D, Hirche A, Klovekorn WP, Schaper J. Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure. European Heart J. 1997; 18:470–479.

    CAS  Google Scholar 

  15. Hein S, Kostin S, Heling A, Maeno Y, Schaper J. The role of the cytoskeleton in heart failure. Cardiovascular Res. 2000; 45:273–278.

    Article  CAS  Google Scholar 

  16. Hein S, Scholz D, Fujitani N, Rennollet H, Brand T, Friedl A, Schaper J. Altered expression of titin and contractile proteins in failing human myocardium. J Mol Cell Cardiol 1994;26:1291–1306.

    Article  CAS  PubMed  Google Scholar 

  17. Schaper J, Froede R, Hein S, Buck A, Hashizume H, Speiser B, Friedl A, Bleese N. Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation 1991;83:504–514.

    CAS  PubMed  Google Scholar 

  18. Schaper J, Speiser B, Brand T. The cytoskeleton and extracellular matrix in human hearts with dilated cardiomyopathy. In: Figulla HR, Kandolf R, McManus B, eds. Idiopathic Dilated Cardiomyopathy. Berlin, Germany: Springer-Verlag; 1993:75–80.

    Google Scholar 

  19. Sharov VG, Sabbah HN, Ali AS, Shimoyama H, Lesch M, Goldstein S. Abnormalities of cardiomyocytes in regions bordering fibrous scars in dogs with chronic heart failure. Int'l J Cardiol 1997;60:273–279.

    CAS  Google Scholar 

  20. Capetanaki A, Milner DJ, Weitzer G. Desmin in muscle formation and maintenance: knockout and consequences. Cell Struct Funct 1997;22:103–116.

    CAS  PubMed  Google Scholar 

  21. Hynes RO. Fibronectins. Berlin, Germany, Springer; 1989.

    Google Scholar 

  22. Schaper J, Hein S, Scholz D, Mollnau H. Multifaceted morphological alterations are present in the failing human heart. J Mol Cell Cardiol 1995;27:857– 861.

    Article  CAS  PubMed  Google Scholar 

  23. Traub P. Intermediate filaments: A review. Berlin, Germany, Springer-Verlag; 1985.

    Google Scholar 

  24. Klein MB, Yalamanchi N, Pham H, Longaker MT, Chan J. Flexor tendon healing in vitro: Effects of TGF-beta on tendon cell collagen production. J Hand Surgery 2002; American Vol 27:615–620.

    Google Scholar 

  25. Weber KT, Brilla CG, Janicki JS. Myocardial Fibrosis: functional significance and regulatory factors. Cardiovascular Res. 1993;27:341–348.

    CAS  Google Scholar 

  26. Sabbah HN, Sharov VG, Goldstein S. Remodeling of the cardiac interstitium in the progression of heart failure. J Clin Basic Cardiol 1999;2:113–116.

    Google Scholar 

  27. Wang N, Ingber DE. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. Biophys J. 1994;66:2181–2189.

    CAS  PubMed  Google Scholar 

  28. Choquet D, Felsenfeld DP, Sheetz MP. Extracellular-matrix rigidity causes strengthening of integrin-cyto- skeleton linkages. Cell 1997;88:39–48.

    Article  CAS  PubMed  Google Scholar 

  29. Yang YG, Obinata T, Shimada Y. Developmental relationship of myosin binding proteins (myomesin, connecting and C-protein) to myosin in chicken somites as studied by immunofluorescence microscopy. Cell Structure and Function 2000;25:177–185.

    Article  CAS  PubMed  Google Scholar 

  30. Commber SJ, Taracewicz E, Akhtar S, deHaan A, Elliott GE. Ion-dependence of Z-line and M-line response to calcium in striated muscle fibers in rigor. Cell Calcium 2001;30:297–309.

    Google Scholar 

  31. Karsanov NV, Jinchvelashvili BG. Conformational state of thin myofilament proteins in normal and chronically failing heart. General Physiology and Biophysics 1990;9:129–145.

    CAS  PubMed  Google Scholar 

  32. Luegmayr E, Glantschnig H, Vagra F, Klaushofer K. The organization of adherens junctions in mouse osteoblast-like cells (MC3T3-E1) and their modulation by triiodothyronine and 1,25-dihydroxyvitamin D3. Histochemistry and Cell Biology 2000;113:467–478.

    CAS  PubMed  Google Scholar 

  33. Kostin S, Hein S, Arnon E, Scholz D, Schaper J. The cytoskeleton and related proteins in the human failing heart. Heart Failure Reviews 2000;5:271–280.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, Michigan, 48202

    Victor G. Sharov M.D., Ph.D., Sawa Kostin M.D., Ph.D., Anastassia Todor M.D., Jutta Schaper M.D. & Hani N. Sabbah Ph.D. (Director)

Authors
  1. Victor G. Sharov M.D., Ph.D.
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  2. Sawa Kostin M.D., Ph.D.
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  3. Anastassia Todor M.D.
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  4. Jutta Schaper M.D.
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  5. Hani N. Sabbah Ph.D.
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Corresponding author

Correspondence to Hani N. Sabbah Ph.D..

Additional information

This study was supported, in part, by grants from the National Heart, Lung, and Blood Institute, RO1-HL49090-09 and PO1 HL074237-03

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Sharov, V.G., Kostin, S., Todor, A. et al. Expression of Cytoskeletal, Linkage and Extracellular Proteins in Failing Dog Myocardium. Heart Fail Rev 10, 297–303 (2005). https://doi.org/10.1007/s10741-005-7544-2

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  • DOI: https://doi.org/10.1007/s10741-005-7544-2

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