Fate of fibrinogen in human arterial intima

Abstract

Fibrinogen and fibrinogen/fibrin-related antigen (total FRA) was measured in human normal intima and different types of atherosclerotic lesions and mural thrombi. The amount showed marked variation between groups of tissue samples, but within each group there was a significant correlation between levels of total FRA and low density lipoprotein (LDL), suggesting that some common factor must influence their influx or retention. The total FRA were analyzed by gradient sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting with antisera to whole fibrinogen and fragments D and E, and fibrinopeptide A (FPA). All intimal samples (but not thrombi) contained fragment X, the first product of plasmin digestion of fibrinogen, but fragment Y was present in only half the samples, and no core-fragment E containing FPA was detected in any sample, suggesting that fibrinogenolysis is limited. By contrast, all samples contained fragment E, which was negative for FPA, so presumably derived from fibrin; they also contained fragments D-dimer and DY, which are characteristic degradation products of cross-linked fibrin. There were no differences between samples obtained during reconstructive vascular surgery and samples obtained at autopsy, so the patterns appear to represent the steady state. This implies that within the intima there is continuous formation of cross-linked fibrin and continuous fibrinolysis, both processes generating fragments that may have atherogenic properties.