Abstract
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.
