Skip to main content
SpringerLink
Log in

Cardiac matrix remodeling following intracoronary cell transplantation in dilated cardiomyopathic rabbits

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Cellular cardiomyoplasty has been proposed as a promising therapeutic strategy for chronic heart failure. Previous studies focused on structural changes in cardiomyocytes to explain the potential benefits for contractile function. However, limited information is available about the cardiac matrix remodeling following cell transplantation in dilated cardiomyopathy (DCM). Here, we established a new animal model of intracoronary bone marrow mononuclear cells (BMMNCs) transplantation to explore extracellular matrix remodeling in adriamycin-induced cardiomyopathic rabbits. In vivo studies demonstrated that BMMNCs transplantation can dramatically delay the progress of collagen metabolism and decrease myocardial collagen volume fraction. The beneficial effects were mediated by attenuating stress-generated over-expression of matrix metalloproteinases (MMPs) in ventricular remodeling. Improved cardiac function may be contributed in part by stem-associated inhibition of extracellular matrix remodeling.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jessup M, Brozena S (2003) Heart failure. N Engl J Med 348:2007–2018

    Article  PubMed  Google Scholar 

  2. Knaapen MW, Davies MJ, De Bie M, Haven AJ, Martinet W, Kockx MM (2001) Apoptotic versus autophagic cell death in heart failure. Cardiovasc Res 51:304–312

    Article  CAS  PubMed  Google Scholar 

  3. Takano H, Hasegawa H, Nagai T, Komuro I (2003) Implication of cardiac remodeling in heart failure: mechanisms and therapeutic strategies. Intern Med 42:465–469

    Article  CAS  PubMed  Google Scholar 

  4. Templin C, Kotlarz D, Marquart F, Faulhaber J, Brendecke V, Schaefer A, Tsikas D, Bonda T, Hilfiker-Kleiner D, Ohl L, Naim HY, Foerster R, Drexler H, Limbourg FP (2006) Transcoronary delivery of bone marrow cells to the infarcted murine myocardium feasibility, cellular kinetics, and improvement in cardiac function. Basic Res Cardiol 101:301–310

    Article  PubMed  Google Scholar 

  5. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H (2006) Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST trial. Circulation 113:1287–1294

    Article  PubMed  Google Scholar 

  6. Nakajima H, Sakakibara Y, Tambara K, Marui A, Yoshimoto M, Premaratne GU, Lin X, Kanemitsu N, Sakaguchi G, Ikeda T, Nishimura K, Nakahata T, Komeda M (2008) Route in bone marrow cell transplantation should be optimized according to the etiology of heart disease. Circ J 72:1528–1535

    Article  PubMed  Google Scholar 

  7. Ishida M, Tomita S, Nakatani T, Fukuhara S, Hamamoto M, Nagaya N, Ohtsu Y, Suga M, Yutani C, Yagihara T, Yamada K, Kitamura S (2004) Bone marrow mononuclear cell transplantation had beneficial effects on doxorubicin-induced cardiomyopathy. J Heart Lung Transplant 23:436–445

    Article  PubMed  Google Scholar 

  8. Jin B, Shi HM, Zhu J, Luo XP, Huang CL, Liu XD, Wang YP, Liu CJ (2007) Experimental study on rabbit dilated cardiomyopathic model. Lab Anim Comp Med 27:77–80

    Google Scholar 

  9. Tomita S, Ishida M, Nakatani T, Fukuhara S, Hisashi Y, Ohtsu Y, Suga M, Yutani C, Yagihara T, Yamada K, Kitamura S (2004) Bone marrow is a source of regenerated cardiomyocytes in doxorubicin-induced cardiomyopathy and granulocyte colony-stimulating factor enhances migration of bone marrow cells and attenuates cardiotoxicity of doxorubicin under electron microscopy. J Heart Lung Transplant 23:577–584

    Article  PubMed  Google Scholar 

  10. Tang J, Xie Q, Pan G, Wang J, Wang M (2006) Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg 30:353–361

    Article  PubMed  Google Scholar 

  11. Rong SL, Lu YX, Liao YH, Wang XL, Wang YJ, Chang C, Wang YQ, Liu QY, Gao YZ, Mi SH (2008) Effects of transplanted myoblasts transfected with human growth hormone gene on improvement of ventricular function of rats. Chin Med J 121:347–354

    CAS  PubMed  Google Scholar 

  12. Binkley PF, Lesinski A, Ferguson JP, Hatton PS, Yamokoski L, Hardikar S, Cooke GE, Leier CV (2008) Recovery of normal ventricular function in patients with dilated cardiomyopathy: predictors of an increasingly prevalent clinical event. Am Heart J 155:69–74

    Article  PubMed  Google Scholar 

  13. Schwartzkopff B, Fassbach M, Pelzer B, Brehm M, Strauer BE (2002) Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy. Eur J Heart Fail 4:439–444

    Article  CAS  PubMed  Google Scholar 

  14. Herpel E, Pritsch M, Koch A, Dengler TJ, Schirmacher P, Schnabel PA (2006) Interstitial fibrosis in the heart:differences in extracellular matrix proteins and matrix metalloproteinases in end-stage dilated, ischaemic and valvular cardiomyopathy. Histopathology 48:736–747

    Article  CAS  PubMed  Google Scholar 

  15. King MK, Coker ML, Goldberg A, McElmurray JH, Gunasinghe HR, Mukherjee R, Zile MR, O’Neill TP, Spinale FG (2003) Selective matrix metalloproteinase inhibition with developing heart failure: effects on left ventricular function and structure. Circ Res 92:177–185

    Article  CAS  PubMed  Google Scholar 

  16. Gilbert SJ, Wotton PR, Bailey AJ, Sims TJ, Duance VC (2000) Alterations in the organisation, ultrastructure and biochemistry of the myocardial collagen matrix in doberman pinschers with dilated cardiomyopathy. Res Vet Sci 69:267–274

    Article  CAS  PubMed  Google Scholar 

  17. Luchner A, Muders F, Dietl O, Friedrich E, Blumberg F, Protter AA, Riegger GA, Elsner D (2001) Differential expression of cardiac ANP and BNP in a rabbit model of progressive left ventricular dysfunction. Cardiovasc Res 51:601–617

    Article  CAS  PubMed  Google Scholar 

  18. Tigen K, Karaahmet T, Kahveci G, Tanalp AC, Bitigen A, Fotbolcu H, Bayrak F, Mutlu B, Basaran Y (2007) N-terminal pro brain natriuretic peptide to predict prognosis in dilated cardiomyopathy with sinus rhythm. Heart Lung Circ 16:290–294

    Article  CAS  PubMed  Google Scholar 

  19. Spiegelstein D, Kim C, Zhang Y, Li G, Weisel RD, Li RK, Yau TM (2007) Combined transmyocardial revascularization and cell-based angiogenic gene therapy increases transplanted cell survival. Am J Physiol Heart Circ Physiol 293:3311–3316

    Article  Google Scholar 

  20. Nagya N, Kangawa K, Itoh T, Iwase T, Murakami S, Miyahara Y, Fujii T, Uematsu M, Ohgushi H, Yamagishi M, Tokudome T, Mori H, Miyatake K, Kitamura S (2005) Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation 112:1128–1135

    Article  Google Scholar 

  21. Hirose S, Takahashi M, Ogawa R, Morimoto H, Izawa A, Sato H, Ise H, Hongo M, Ikeda U (2007) Erythropoietin attenuates the development of experimental autoimmune myocarditis. Cardiovasc Drugs Ther 21:17–27

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge Dr. Ying Shan for her editorial suggestions for the article. This study was supported in part by the 11th Five-year National Science Project on Chronic Heart Failure in China (2006BAI01A04).

Author information

Authors and Affiliations

  1. Department of Cardiology, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China

    Bo Jin, Xin-Ping Luo, Huan-Chun Ni, Yong Li & Hai-Ming Shi

Authors
  1. Bo Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin-Ping Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huan-Chun Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hai-Ming Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hai-Ming Shi.

Additional information

Bo Jin and Xin-Ping Luo have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jin, B., Luo, XP., Ni, HC. et al. Cardiac matrix remodeling following intracoronary cell transplantation in dilated cardiomyopathic rabbits. Mol Biol Rep 37, 3037–3042 (2010). https://doi.org/10.1007/s11033-009-9874-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-009-9874-y

Keywords

Search

Navigation