The role of vitronectin receptor (alphavbeta3) 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 alphavbeta3.

BACKGROUND

The vitronectin receptor (integrin alphavbeta3) 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 alphavbeta3 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 alphavbeta3 (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, alphavbeta3 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 alphavbeta3. The significant correlation of alphavbeta3 with cellular rejection suggests an important role for this integrin in serving as a mechanistic link between cellular rejection and vasculopathy.