In situ detection of tissue factor within the coronary intima in rat cardiac allograft vasculopathy

Cardiac allograft vasculopathy is a major cause of morbidity and mortality of cardiac transplant recipients. The underlying cause of this disease rema ins unclear. Histological studies have implicated accelerated hemostasis an d intravascular fibrin deposition in its pathogenesis. In the present study a defined model of this disease in the rat mas used to elucidate the impli cation of tissue factor in the production of the hypercoagulable state obse rved in cardiac allograft vessels. Tissue factor protein and mRNA expressio n were studied in rat heart allografts developing allograft vasculopathy re sembling human disease. Immunohistochemistry demonstrated tissue-factor-pos itive cells present in the allograft coronary intima and adventitia. Signif icant staining for tissue factor mas detected in the endothelium lining cor onary lesions in cardiac allografts and in interstitial mononuclear cells, respectively. Both transplant coronary endothelial cells and mononuclear ce lls contained tissue factor mRNA as indicated by oligo-cell reverse transcr iption polymerase chain reaction after laser-assisted cell picking. In cont rast, tissue factor mRNA and protein were not or negligibly dectectable wit hin the coronary intima of nontransplanted control hearts. Thus, the presen t study clearly demonstrates that aberrant tissue factor expression occurs within the coronary intima after cardiac transplantation. Tissue factor, ac tivating downstream coagulation mechanisms, may account for the intravascul ar clotting abnormalities observed in cardiac allografts and may represent a key factor in transplant atherogenesis.