Acute vascular rejection is associated with up-regulation of vitronectin receptor (αvβ3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system

Mohamad H. Yamani, Randall C. Starling, James B. Young, Daniel Cook, Yang Yu, D. Geoffrey Vince, Patrick McCarthy, Norman B. Ratliff

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of vitronectin receptor (αvβ3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. Methods: Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for αvβ3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). Results: Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of αvβ3 (1.9-fold, p < 0.001), tissue factor (1.8-fold, p < 0.001), and EMMPRIN (1.5-fold, p < 0.001). All patients in the AVR group received plasmapheresis; 11 of 14 patients had evidence of ischemic necrosis on biopsy specimens, and 3 of 14 patients experienced hemodynamic compromise and graft dysfunction and died within 3 weeks of transplant. Another patient died at 10 months after transplant. Conclusions: Acute vascular rejection is associated with up-regulation of αvβ3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.

Original languageEnglish (US)
Pages (from-to)983-989
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2002

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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