title: Myocardial ischemic injury after heart transplantation is associated with upregulation of vitronectin receptor (alpha(v)beta3), activation of the matrix metalloproteinase induction system, and subsequent development of coronary vasculopathy.
abstract: BACKGROUND
  Myocardial ischemic injury after heart transplantation is associated with subsequent development of graft vasculopathy. Both vitronectin receptor (integrin alpha(v)beta3) and tissue factor play key roles in vascular endothelial cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury models.
  
  
  RESULTS
  Thirteen patients developed myocardial ischemic injury within 2 weeks of cardiac transplantation (ischemia group). These were compared with 10 transplantation patients who had no evidence of ischemia (control group). Endomyocardial biopsies were evaluated within 2 weeks of transplantation for alpha(v)beta3, tissue factor, and extracellular MMP inducer (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis was quantified. All patients underwent intravascular ultrasound at 1 month and 1 year after transplantation. Compared with control, the ischemia group demonstrated evidence of significant increased expression of alpha(v)beta3 (3.2-fold, P<0.001), tissue factor (2.5-fold, P<0.001), and EMMPRIN (1.9-fold, P=0.01). At 1 year, the ischemia group had a significant increase in myocardial fibrosis (24+/-1.8% versus 14+/-1.1%, P<0.001) and zymographic activity of MMP-2 (1.4-fold, P<0.001), MMP-3 (1.2-fold, P<0.001), and MMP-9 (1.3-fold, P=0.01). Coronary vasculopathy progression was also more advanced in the ischemia group (change in coronary maximal intimal thickness over 1 year 0.54+/-0.1 versus 0.26+/-0.06 mm; P=0.031).
  
  
  CONCLUSIONS
  Myocardial ischemic injury after cardiac transplantation is associated with upregulation of alpha(v)beta3, tissue factor, and activation of the MMP induction system, which may contribute to the subsequent development of allograft remodeling and vasculopathy.
authors: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Ohio 44195, USA. yamanim@ccf.org
authors: Mohamad H
authors: MH
authors: Yamani
authors: E Murat
authors: EM
authors: Tuzcu
authors: Randall C
authors: RC
authors: Starling
authors: Norman B
authors: NB
authors: Ratliff
authors: Yang
authors: Y
authors: Yu
authors: D Geoffrey
authors: DG
authors: Vince
authors: Kimerly
authors: K
authors: Powell
authors: Daniel
authors: D
authors: Cook
authors: Patrick
authors: P
authors: McCarthy
authors: James B
authors: JB
authors: Young
mesh_terms: D000328:Adult; D018450:Disease Progression; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D019030:Receptors, Vitronectin / Q000096:biosynthesis* / Q000276:immunology; D013925:Thromboplastin / Q000096:biosynthesis / Q000276:immunology; D014463:Ultrasonography; D015854:Up-Regulation
chemical_list: D019030:Receptors, Vitronectin; D013925:Thromboplastin; D020782:Matrix Metalloproteinases