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

Objectives 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. Methods 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. Key finding 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‐HDL₃ 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. Conclusion 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.