Influence of atorvastatin on fractional and subfractional composition of serum lipoproteins and MMP activity in mice with Triton WR 1339-induced lipaemia.

The effects of atorvastatin on the atherogenic and anti-atherogenic lipoprotein-cholesterol (C-LP) and lipoprotein-triglyceride (TG-LP) fractions and subfractions at the early stage of murine acute hyperlipidaemia, and its pleiotropic anti-inflammatory effects via the activity of matrix metalloproteinases (MMPs) were studied. Atorvastatin (75 mg/kg) was administered to ICR mice with acute lipaemia induced by a single injection of Triton WR 1339 (500 mg/kg). A novel small-angle X-ray scattering (SAXS) method was used for the determination of the fractional and subfractional composition of C-LP and TG-LP. In Triton WR 1339-treated mice, there was a drastic increase in the atherogenic low-density C-LP (C-LDL) fraction, intermediate density lipoprotein-cholesterol (C-IDL) subfraction, and very low-density C-LP (C-VLDL) fractions (C-VLDL(3-5) subfraction). Additionally, there was an increase in the C-HDL(3) subfraction. Treatment of lipaemia with atorvastatin resulted in the normalization of the atherogenic C-LDL fraction and the C-IDL subfraction. A decrease in C-VLDL (C-VLDL(3-5) subfraction), total cholesterol and, especially, triglyceride (TG) concentrations was also demonstrated. Similar results were obtained with the TG-LP fractions and subfractions. Additionally, atorvastatin treatment resulted in an increase in the serum and liver MMP activity. High-dose atorvastatin therapy exerts its rapid lipid-lowering and pleiotropic effect(s) in the early stages of acute lipaemia induced with Triton WR-1339.