The role of vitronectin receptor (αv/β3) and tissue factor in the pathogenesis of transplant coronary vasculopathy

OBJECTIVES: This study was undertaken to test the hypothesis that transplant coronary vasculopathy (CV) is associated with increased myocardial protein expression of both tissue factor (TF) and integrin αv/β3. BACKGROUND: The vitronectin receptor (integrin αv/β3) and TF have recently been found to play a key role in apoptotic cell death and vascular endothelial cell injury. METHODS: A total of 77 heart transplant recipients underwent simultaneous endomyocardial biopsy and intravascular ultrasound (IVUS) at one year of transplant. Patients with pre-existing donor coronary atherosclerosis (n = 35) or with acute rejection (grade >1A, n = 10) at the time of the IVUS were excluded from the analysis. The remaining 32 patients constitute the cohort of the present study. A computerized biopsy score was derived based on the duration and severity of cellular rejection. Both TF and αv/β3 expression in the heart biopsy specimens were evaluated by immunoperoxidase histochemistry and Western blot analysis. RESULTS: Patients with CV (n = 24) had increased expression of αv/β3 (2.7-fold, p = 0.003) and TF (7.9-fold, p = 0.04) compared with patients without evidence of vasculopathy (n = 8). In the absence of myocardial fibrosis, αv/β3 expression correlated significantly with the cellular rejection score (r = 0.58, p = 0.02). CONCLUSIONS: Transplant vasculopathy is associated with increased expression of both TF and αv/β3. The significant correlation of αv/β3 with cellular rejection suggests an important role for this integrin in serving as a mechanistic link between cellular rejection and vasculopathy.