Effects of gene transfection of human bcl-2 on concordant cardiac xenografts in hamster to rat model.

ABSTRACT

OBJECTIVES: Concordant cardiac xenografts are known for delayed vascular rejection. Therapy combining with FK506 and cobra venom factor prolongs graft survival. The proposed underlying mechanism holds that cytoprotective proteins such as Bcl-2 play a role here. We studied the effects of gene transfection of human-bcl-2 on graft survival and coronary artery lesions in concordant cardiac xenografts, and discuss the role of cytoprotective genes in vascular xenograft rejection. METHODS: Golden-Syrian-hamster hearts were heterotopically transplanted into Lewis rats given FK506 (1 mg/kg daily) and cobra venom factor (0.2 mg/kg; day 0 and 1) intramuscularly. They were divided into 2 groups--grafts transfected vector with the human-bcl-2 gene (Group-B(+)) and vector without the gene (Group-B(-)) using the HVJ liposome method; 4 or 5 grafts from each group were explanted 1, 2, 3, or 4 weeks and more than 1 month after transplantation and evaluated by H-E, Elastic-Van-Gieson and immunohistochemical staining of Bcl-2. Coronary arterial lesions were examined using a scoring method. RESULTS: Bcl-2 expression in endothelial cells in Group-B(+) was confirmed within 2 weeks after transplantation but not thereafter. The coronary score in Group-B(+) was significantly lower than that in Group-B(-) within 2 weeks after transplantation but not thereafter. CONCLUSIONS: In this hamster-to-rat cardiac xenograft model, the bcl-2 gene was successfully transfected to the coronary endothelium and lasted 2 weeks. During Bcl-2 expression, coronary vascular lesions were suppressed more than in the untransfected group.