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

Mohamad H. Yamani, Carolina S. Masri, Norman B. Ratliff, Meredith Bond, Randall C. Starling, E. Murat Tuzcu, Patrick M. McCarthy, James B. Young

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26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)804-810
Number of pages7
JournalJournal of the American College of Cardiology
Volume39
Issue number5
DOIs
StatePublished - Mar 6 2002

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Yamani, M. H., Masri, C. S., Ratliff, N. B., Bond, M., Starling, R. C., Tuzcu, E. M., McCarthy, P. M., & Young, J. B. (2002). The role of vitronectin receptor (αv/β3) and tissue factor in the pathogenesis of transplant coronary vasculopathy. Journal of the American College of Cardiology, 39(5), 804-810. https://doi.org/10.1016/S0735-1097(01)01823-X