Haemostatic factors in human aortic intima.
Accumulation of lipid in developing fibrous atherosclerotic plaques is associated with high concentrations of fibrin and accumulation of a tightly bound lipoprotein fraction that can be released by incubation with fibrinolytic enzymes, suggesting that fibrin may play a key role in lesion development. It is not known whether this fibrin represents incorporated mural thrombus or is produced in situ by clotting of the fibrinogen that is present in intima in high concentration. Immunoelectrophoresis was used to measure the concentrations of fibrinogen and components of the clotting system in human aortic intima and lesions, and in mural thrombi. In the lipid and fibrin rich plaque centres prothrombin concentration was almost twice that in normal intima, but concentrations of the thrombin inhibitors antithrombin III and alpha 2-macroglobulin fell, so that the molar ratios of inhibitor/prothrombin fell from 3:1 in normal intima to 1:1 in the plaque centre. In mural thrombi there was preferential sequestration of fibrinogen-like antigen and prothrombin. Distribution of factor-VIII-related antigen was highly unpredictable; in both normal intima and all types of intimal lesion substantial amounts were recovered from some samples, whereas none was recovered from others. The highest concentrations were found in samples free of endothelium from the deep layers of lesions. The results are compatible with the idea that fibrinogen may be converted to fibrin within lesions; once some fibrin has accumulated within the intima it seems to bind low-density lipoprotein and sequester fibrinogen and clotting factors, thereby producing a self-amplifying system.
D000368:Aged; D001011:Aorta / Q000378:metabolism*; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006490:Hemostatics / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000378:metabolism
D001798:Blood Proteins; D006490:Hemostatics; D008077:Lipoproteins, LDL; D011516:Prothrombin; D005169:Factor VIII; D005337:Fibrin; D005340:Fibrinogen