title: Influence of atorvastatin on fractional and subfractional composition of serum lipoproteins and MMP activity in mice with Triton WR 1339-induced lipaemia.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Physiology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Timakov, Russia. t.a.korolenko@physiol.ru
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Korolenko
authors.forename: Marina S
authors.initials: MS
authors.lastname: Cherkanova
authors.forename: Fedor V
authors.initials: FV
authors.lastname: Tuzikov
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Johnston
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Tuzikova
authors.forename: Viktoriya M
authors.initials: VM
authors.lastname: Loginova
authors.forename: Vassilij I
authors.initials: VI
authors.lastname: Kaledin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood*; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D011092:Polyethylene Glycols; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D053838:Scattering, Small Angle; D014280:Triglycerides / Q000097:blood; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D011758:Pyrroles; D014280:Triglycerides; D011092:Polyethylene Glycols; D002784:Cholesterol; D000069059:Atorvastatin; D020782:Matrix Metalloproteinases; C016811:tyloxapol