title: Acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system.
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 (alphavbeta3), 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 alphavbeta3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN).
  
  
  RESULTS
  Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of alphavbeta3 (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 alphavbeta3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.
authors.affiliation: Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA. yamanim@ccf.org
authors.forename: Mohamad H
authors.initials: MH
authors.lastname: Yamani
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.forename: Daniel
authors.initials: D
authors.lastname: Cook
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: D Geoffrey
authors.initials: DG
authors.lastname: Vince
authors.forename: Patrick
authors.initials: P
authors.lastname: McCarthy
authors.forename: Norman B
authors.initials: NB
authors.lastname: Ratliff
mesh_terms: D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051926:Basigin; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D009336:Necrosis; D019030:Receptors, Vitronectin / Q000276:immunology*; D013925:Thromboplastin / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C497886:BSG protein, human; D008562:Membrane Glycoproteins; D019030:Receptors, Vitronectin; D051926:Basigin; D013925:Thromboplastin