[The role of fibrinogen in the pathogenesis of artherosclerosis and the mechanisms of its action].

On rabbit artherosclerosis (AS) model induced by feeding high-cholesterol, we found that the level of plasma fibrinogen (Fg) was increased early. There was a positive correlation between the level of plasma Fg and cholesterol. By means of immunohistology analysis in vascular AS plaque, it was found that Fg and its degradation products were diffusely distributed beneath endothelium and in vascular matrix. Fg itself and its soluble metabolic products did not stimulate the proliferation of cultured vascular smooth muscle cell (SMC), but insoluble fibrin (Fb) converted from Fg stimulated SMC growth, collegen synthesis, intracellular cholesterol accumulation and endothelin release in a dose-dependent manner. In addition, Fg inhibited NO synthesis. The results suggest that Fb is an important pathogenetic factor of AS. Our studies also showed that the effect of Fb on SMC growth was dependent on extracellular Ca2+ and was mediated by protein kinase C pathway.