Systemic activation of integrin α_vβ3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient

Background: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin α_Vβ3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of α_Vβ3 in the donor before transplantation. Methods: We evaluated mRNA expressions of α_Vβ3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of α_Vβ3 was present in the donor before transplantation, α_Vβ3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group. Results: The ICH Group showed significant increased mRNA expression of α_Vβ3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic α_Vβ3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03). Conclusions: Our report demonstrates the presence of systemic activation of α_Vβ3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient.