Interaction of plasma proteins especially fibrin and its degradation products in the production of proliferative atherosclerotic lesions
The primary aim of this thesis was to investigate the interaction of plasma proteins especially fibrin and its degradation products in the production of proliferative atherosclerotic lesions. Several factors have been considered, in isolation, and within the atherosclerotic lesions, these are fibrinogen, fibrin, fibrin degradation products, thrombin, plasmin, fibronectin and platelets. To attempt this task several approaches were utilized. The ability of the factors under consideration to stimulate cell proliferation was assessed by the use of the chick chorioallantoic membrane (CAM). Plasmin, platelets, fibronectin, fibrinogen and surprisingly serum were found not to cause any cell proliferative stimulation of the CAM. Plasma, fibrin degradation products, thrombin and intimal extracts were shown to produce cell proliferation. Use of affinity columns indicated that stimulatory activity found within the lesions was due to fibrin degradation products. Thrombin experiments indicated that its stimulatory activity was due to coagulation followed by fibrinolysis. Further studies indicated that the active fraction within fibrin degradation products and intimal lesion extracts was due to fibrin fragment E. This was shown by several approaches, long plasmin digests of fibrin, thrombin treatment of commercial fragment E to form fibrin 'like' fragment E, affinity columns for fibrinogen fragment D and fragment E, and blocking of activity by use of a fibrin fragment E polyclonal antibody. The final chapter is a summary of the important findings in this study, suggesting where fibrin fragment E may fit into the initiation of the cell proliferative response, and possible clinical relevance of these findings.