TGF-B2 expression and association with stress proteins in allogeneic vs. syngeneic peripheral vessel allografts over time

Abstract

Introduction: In prior studies transplanted peripheral vessels in allogeneic rats had increasing amounts of fibroplasia and hyperplasia with time, associated with chronic rejection. We previously reported on the increased expression of TGF-b2 in a peripheral vessel model. We hypothesized that TGF-b2 expression is linked to expression of Caspace-3 and HSP60 and 70. Methods: Lewis rats served as recipients for femoral artery grafts using Lewis (syngeneic) and Brown-Norway (allogeneic) donors. Vessels were harvested at various times. Each vessel was fixed and immunostained for TGF-b2, Caspace-3, and HSP60 and 70. Image analysis was used to quantify the data. Results were then analyzed using Two Way ANOVA. Results: There was a unique rejection response in the allogeneic transplants, in which initial vessel necrosis is followed by intimal hyperplasia. There was a statistically significant difference among expression of TGF-b2 and Caspace-3 in the allogeneic grafts as compared to the syngeneic grafts. The greatest expression occurred at 25 days in both groups (p < 0.001 for TGF-b2, p = 0.029 for Caspace-3). There was an inverse relationship between TGF-b2 and HSP70 expression over time, with a greater level of HSP70 expression in the syngeneic grafts. There was no significant difference between TGF-b2 expression and HSP60 levels in the two groups, as concentrations of HSP60 remained constant over time. Conclusions: In conclusion, TGF-b2 plays a role in fibroplasia associated with chronic rejection in a peripheral vessel transplant model, possibly related to apoptosis via Caspace-3 expression, and HSP70 expression.