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The clinical investigator

, Volume 70, Issue 9, pp 780–790 | Cite as

Towards understanding the pathophysiology of chronic rejection

  • P. Häyry
  • A. Mennander
  • S. Yilmaz
  • J. Ustinov
  • A. Räisänen
  • A. Miettinen
  • I. Lautenschlager
  • K. Lemström
  • C. A. Bruggeman
  • T. Paavonen
Guest Lecture, “Gesellschaft für Nephrologie”, 23rd Congress

Summary

Chronic allograft rejection is the major reason why allografts are lost. While only 2%-3% of all allografts are lost during the first year to irreversible acute rejection, approximately 6%–7% are lost during each subsequent year to chronic rejection. The major manifestation of chronic rejection in all organs is persistent perivascular inflammation and allograft arteriosclerosis. Bearing this in mind, we have developed a model to investigate the pathophysiology of allograft arteriosclerosis using aortic transplantations between inbred rat strains. The results obtained thus far indicate that several different inflammatory cascades are operative within the vascular wall during allograft arteriosclerosis. The relative importance of these different cascades, and particularly the role of growth factors as final effectors, has not yet been defined. Attempts to suppress allograft arteriosclerosis under experimental conditions have already met with some success: under conditions where no immunosuppression is provided we have been able to delay the process by at least 3 months, though we have not been able to block it indefinitely. It may be expected, however, that once the inflammatory cascades leading to smooth muscle cell replication in the allograft media and their influx into the intima are better defined, more specific approaches to the inhibition of allograft arteriosclerosis will be developed.

Key words

Allograft arteriosclerosis Chronic allograft rejection Growth factors Smooth muscle cell replication 

Abbreviations

ATG

antilymphocyte globulin

CMV

cytomegalovirus

CyA

cyclosporine

LT

leukotriene

PCR

polymerase chain reaction

pfu

plaque-forming units

RCMV

rat cytomegalovirus

RIA

radioimmunoassay

TxB2a

thromboxane B2

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • P. Häyry
    • 1
  • A. Mennander
    • 1
  • S. Yilmaz
    • 1
  • J. Ustinov
    • 1
  • A. Räisänen
    • 1
  • A. Miettinen
    • 1
  • I. Lautenschlager
    • 1
  • K. Lemström
    • 1
  • C. A. Bruggeman
    • 1
  • T. Paavonen
    • 1
  1. 1.Transplantation LaboratoryUniversity of HelsinkiFinland

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