Skip to main content
SpringerLink
Log in

Transplant Vasculopathy

Transplantatvaskulopathie

  • Published:
Herz Aims and scope Submit manuscript

Abstract

Transplant vasculopathy constitutes the major impediment to long-term survival in heart transplant recipients. Within the “response to immune injury” paradigm, it can best be understood as the resultant of an orchestrated recipient immune response to the initial allogenic stimulus by graft vascular endothelium. This response incorporates the elaboration of complex coordinated cytokine patterns and corresponding cell types including B-lymphocytes, T_helperl_ and T_helper2_cells, cytotoxic T-cells, macrophages, and polymorphonuclear cells. These attack the alloantigenic vascular endothelium and lead, by complex cytokine signalling, to migration of donor smooth muscle cells from the media into the intima, associated with a switch from the contractile to a synthetic phenotype. In conjunction with recipient T-cells, macrophages, and lipids, the intimal fibroproliferative growth of the donor vessel is hereby initiated.

Zusammenfassung

Die Transplantatvaskulopathie stellt die Haupttodesursache im Langzeitverlauf nach Herztransplantation dar. Innerhalb des “response to immune injury”-Paradigmas kann sie am besten verstanden werden als Ergebnis einer koordinierten Immunantwort des Empfängers auf den initialen allogenen Stimulus durch das Gefäßendothel des Transplantats. Diese Antwort umfaßt die Generierung komplexer Zytokinmuster und korrespondierender Zelltypen unter Einschluß von B-Zellen, T_Helfer-1_ and T_helper22_cZellen, zytotoxischen T-Zellen, Makrophagen und polymorphkernigen Zellen. Diese attackieren das alloantigene Gefäßendothel und führen über komplexe Zytokinsignale zur Wanderung von glatten Muskelzellen des Spenders von der Media in die Intima, verbunden mit einem Wechsel vom kontraktilen zum synthetischen Phänotyp. In Verbindung mit T-Zellen und Makrophagen des Empfängers sowie Lipiden wird hierdurch das fibroproliferative Wachstum in der Intima des Spendergefäßes initiiert.

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

Similar content being viewed by others

References

  1. Billingham ME. Histopathology of graft coronary disease. J Heart Lung Transplant 1992;11:S38–44.

    Google Scholar 

  2. Billingham ME. Pathology of graft vascular disease after heart and heart-lung transplantation and its relationship to obliterative bronchiolitis. Transplant Proc 1995;27:2013–6.

    PubMed  CAS  Google Scholar 

  3. Costanzo MR, Naftel DC, Pritzker MR, et al. Heart transplant coronary artery disease detected by angiography: a multi-institutional study (abstract). J Heart Lung Transplant 1996;15:S39.

    Google Scholar 

  4. Deng MC, Bell S, Hue P, et al. Cardiac allograft vasculopathy: Relationship to microvascular cell surface markers and inflammatory cell phenotypes on endomyocardial biopsy. Circulation 1995;91:1647–54.

    PubMed  CAS  Google Scholar 

  5. Deng MC, Haverich A, Hunt SA, et al. Management before and after heart transplantation in Germany: Results of two national surveys. Tx Med 1997;9:188–91.

    Google Scholar 

  6. Dong C, Wilson JE, Winters GL, et al. Human transplant coronary artery disease: pathological evidence for Fas-mediated apoptotic cytotoxicity in allograft arteriopathy. Lab Invest 1996;74:921–931.

    PubMed  CAS  Google Scholar 

  7. Gao SZ, Hunt SA, Schroeder JS, et al. Early development of accelerated graft coronary artery disease: risk factors and outcome. J Am Coll Cardiol 1996;28:673–9.

    Article  PubMed  CAS  Google Scholar 

  8. Günther F, Schwammenthal E, Rahmel A, et al. Erste Erfahrungen mit der Dobutamin-Belastungsechokardiographie bei herztransplantierten Patienten. Z Kardiol 1995;84:411–418

    PubMed  Google Scholar 

  9. Gibbons GH. The pathogenesis of graft vascular disease: implications of vascular remodelling. J Heart Lung Transplant 1995;14:S149–58.

    Google Scholar 

  10. Halle AA III, DiSciascio G, Massin EK, et al. Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients. J Am Coll Cardiol 1995;26:120–8.

    Article  PubMed  Google Scholar 

  11. Hosenpud JD, Novick RJ, Bennett LE, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirteenth Official Report-1996. J Heart Lung Transplant 1996;15:655–74.

    PubMed  CAS  Google Scholar 

  12. Hruban RH, Long PP, Perlman EJ, et al. Fluorescence in situ hybridization for the Y-chromosome can be used to detect cells of recipient origin in allografted hearts following cardiac transplantation. Am J Pathol 1993;142:975–80.

    PubMed  CAS  Google Scholar 

  13. Kerber S, Heinemann-Vechtel O, Günther F, et al. Coronary compliance in patients following orthotopic heart transplantation. An intravascular ultrasound study. Eur Heart J 1996;17:1891–7.

    PubMed  CAS  Google Scholar 

  14. Knieriem HJ. Transplantatvaskulopathie-pathogenesekonzepte Update 1996. Z. Herz Thorax Gefäßchir 1997;11:37–43.

    Article  Google Scholar 

  15. Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 1995;333:621–7.

    Article  PubMed  CAS  Google Scholar 

  16. Labarrere CA, Pitts D, Nelson DR, et al. Vascular tissue activator and the development of coronary artery disease in heart transplant recipients. N Engl J Med 1995;333:111–6

    Article  Google Scholar 

  17. McManus BM, Horley KJ, Wilson JE, et al. Prominence of coronary arterial wall lipids in human heart allografts. Am J Pathol 1995;147:293–308.

    PubMed  CAS  Google Scholar 

  18. Mehra MR, Ventura HO, Smart FW, et al. An intravascular ultrasound study of the influence of angiotensin-converting enzyme inhibitors and calcium entry blockers on the development of cardiac allograft vasculopathy. Am J Cardiol 1995;75:853–4.

    Article  PubMed  CAS  Google Scholar 

  19. Meiser BM, Billingham ME, Morris RE. Effects of cyclosporin, FK506, and rapamycin on graft-vessel disease. Lancet 1991;338:1297–8.

    Article  PubMed  CAS  Google Scholar 

  20. Mohacsi PJ, Tüller D, Hulliget B, et al. Different inhibitory effects of immunosuppressive drugs on human and rat aortic smooth muscle and endothelial cell proliferation stimulated by platelet-derived growth factor or endothelial cell growth factor. J Heart Lung Transplant 1997;16:484–92.

    PubMed  CAS  Google Scholar 

  21. Opelz G, Wujciak T, for the Collaborative Transplant Study. The influence of HLA compatibility on graft survival after heart transplantation. N Engl J Med 1994;330:816–9.

    Article  PubMed  CAS  Google Scholar 

  22. Park JW, Merz M, Braun P. Regression of transplant coronary artery disease during chronic low-density lipoprotein-apheresis. J Heart Lung Transplant 1997;16:290–7.

    PubMed  CAS  Google Scholar 

  23. Rickenbacher PR, Pinto FJ, Chenzbraun A, et al. Incidence and severity of transplant coronary artery disease early and up to 15 years after transplantation as detected by intravascular ultrasound. J Am Coll Cardiol 1995;25:171–7.

    Article  PubMed  CAS  Google Scholar 

  24. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990’s. Nature 1993;362:801–9.

    Article  PubMed  CAS  Google Scholar 

  25. Russell ME, Wallace AF, Wyner LR, et al. Upregulation and modulation of inducible nitric oxide synthase in rat cardiac allografts with chronic rejection and transplant arteriosclerosis. Circulation 1995;92:457–64.

    PubMed  CAS  Google Scholar 

  26. Scheidt Wv, Koglin J, Weis M, et al. Epicardial and microvascular manifestations of transplant vasculopathy: two distinct entities (abstract). J Heart Lung Transplant 1997;16:85.

    Google Scholar 

  27. Schmid C, Kerber S, Baba H, et al. Graft vascular disease after heart transplantation. Eur Heart J 1997;18:554–9.

    PubMed  CAS  Google Scholar 

  28. Schmid C, Heemann U, Azuma H, et al. Rapamycin inhibits transplant vasculopathy in long-surviving rat heart allograft. Transplantation 1995;60:729–33.

    Article  PubMed  CAS  Google Scholar 

  29. Schroeder JS, Gao SZ, Aldermann EI, et al. A preliminary study of diltiazem in the prevention of coronary artery disease in heart transplant recipients. N Engl J Med 1993;328:164–70.

    Article  PubMed  CAS  Google Scholar 

  30. Smith JD, Pomerance A, Burke M, et al. Effect of HLA matching on graft function and long-term survival after heart transplantation: results of a large single center study (abstract). J Heart Lung Transplant 1995;14:S40.

    Google Scholar 

  31. Weis M, Scheidt Wv. Cardiac allograft vasculopathy. A review. Circulation 1997;96:2067–77.

    Google Scholar 

  32. Valantine HA, Pinto FJ, St. Goar FG, et al. Intracoronary ultrasound imaging in heart transplant recipients: The Stanford experience. J Heart Lung Transplant 1992;11:S60–4

    Google Scholar 

  33. Yeung AC, Davis SF, Hauptmann PJ, et al. Incidence and progression of transplant coronary disease over 1 year: results of a multicenter trial with use of intravascular ultrasound. J Heart Lung Transplant 1995;14:S215–20.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Muenster University Hospital, Münster, Germany

    Mario C. Deng, Tonny D. T. Tjan, Boulos Asfour, Norbert Roeder & Hans H. Scheld

Authors
  1. Mario C. Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tonny D. T. Tjan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Boulos Asfour
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Norbert Roeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans H. Scheld
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario C. Deng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Deng, M.C., Tjan, T.D.T., Asfour, B. et al. Transplant Vasculopathy. Herz 23, 197–201 (1998). https://doi.org/10.1007/BF03044606

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03044606

Key Words

Schlüsselwörter

Search

Navigation