Expression of Fibrinogen mRNA in the Liver in Triton WR-1339-induced hyperlipidemic rats

The time course of fibrinogen mRNA expression in liver and plasma coagulative and fibrinolytic activities were examined in rats in which hyperlipidemia had been induced by Triton WR-1339. After injection of Triton WR-1339 (300 mg/ kg) into the tail vein of Sprague-Dawley rats, plasma lipid levels, especially of triglyceride (TG) and VLDL-TG, increased from 1 hr to 48 hr. Plasma fibrinogen, a major coagulative factor, tended to accumulate at 1 hr, significantly decreased at 3 hr and increased again at 24 hr after Triton WR-1339 treatment. The levels of β-chain fibrinogen mRNA increased quickly to 3 hr to markedly higher levels than those of α- and γ-chain fibrinogen, and then decreased from 12 to 24 hr. Moreover, Triton WR-1339 caused a significant decrease in plasma levels of α2-plasmin inhibitor, plasminogen and antithrombin III, a slight increase in the plasma tissue-type plasminogen activator level at 24 hr, and a significant increase in the plasma interleukin-6 level at 3 hr and 6 hr. Triton WR-1339-induced hypertriglyceridemia and hyperfibrinogenemia were therefore associated with changes in a-chain fibrinogen mRNA levels that were negatively correlated with the plasma fibrinogen levels.Accordingly, β-chain synthesis appears to be the rate-limiting step in the synthesis of fibrinogen in liver cells and IL-6 might be involved in the regulation of plasma fibrinogen levels in Triton WR-1339-treated rats. Therefore, Triton WR-1339-treated rats with hyper-triglyceridemia and hyperfibrinogenemia may be a suitable model for studying vascular disease that is characterized by these changes.