ABSTRACT
To clarify the mechanisms by which Triton WR-1339 causes an elevation in the plasma fibrinogen level, we studied the time courses of hepatic mRNA expression for beta-chain fibrinogen, interleukin-6 (IL-6) and IL-6 receptor (R) by RT-PCR. After intravenous injection of Triton WR-1339 (150, 300 and 500 mg/kg) in Sprague-Dawley rats, the plasma level of fibrinogen and MCP-1 significantly and dose-relatedly increased from 12 to 24 hours (h). At 3 and 6 hours dose dependent increases were found in hepatic IL-6 and IL-6R mRNA expression with increases in the hepatic mRNA expression for beta-chain fibrinogen as the rate-limiting step in fibrinogen synthesis. These results suggest that the increase in the plasma fibrinogen level is followed by the enhancement of hepatic mRNA expression of beta-chain fibrinogen, IL-6 and IL-6R, that is, IL-6 and IL-6R may partly regulate the plasma fibrinogen level in Triton WR-1339-induced hyperlipidemic rats.
Subject(s)
Fibrinogen/biosynthesis , Hyperlipidemias/blood , Interleukin-6/metabolism , Liver/metabolism , Polyethylene Glycols , Receptors, Interleukin-6/metabolism , Animals , Disease Models, Animal , Female , Hyperlipidemias/chemically induced , Hyperlipidemias/pathology , Interleukin-6/genetics , Liver/drug effects , Liver/pathology , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Interleukin-6/genetics , Surface-Active Agents , Time FactorsABSTRACT
Coagulation activity in KK mice and KK-Ay mice produced by transferring the yellow obese gene (Ay) into KK mice, was studied to examine whether both mice are useful as a model of diabetic atherosclerosis. Plasma levels of hemoglobin A1c (HbA1c), insulin, fibrinogen, plasminogen activator inhibitor (PAI) and thrombomodulin were significantly high in KK and KK-Ay mice compared with age-matched non-diabetic mice (ddY mice). The changes in the plasma levels of fibrinogen at each time-point correlated with the increases in HbA1c levels. Pathological observation by Oil red O staining of aorta tissue from 4-month-old KK and KK-Ay mice revealed the early stages of atherosclerosis such as lipid deposition. These age-related increases in the plasma level of fibrinogen and PAI suggested that KK-Ay mice may contribute to help elucidate the early stages of diabetic atherosclerosis.
