Atorvastatin has distinct effects on endothelial markers in different mouse models of atherosclerosis

J Pharm Pharm Sci. 2006;9(2):222-30.

Abstract

Purpose: Atherosclerosis is a progressive process that initially involves endothelial dysfunction. We investigated the effects of atorvastatin on both lipid parameters, and VCAM-1 and ICAM-1 expression in apoE-deficient or wild type C57BL/6J mice.

Methods: The C57BL/6J mice were fed with either chow or an atherogenic diet for 12 weeks. Male apoE-deficient mice were fed with the chow diet for 12 weeks. In 3 atorvastatin treated groups mice were fed the same diet as described above except atorvastatin was added to the diet at the dosage of 10 mg/kg per day for the last 8 weeks before euthanasia.

Results: Biochemical analysis showed that atorvastatin significantly decreased total cholesterol levels and VLDL in C57BL/6J mice fed with atherogenic diet but increased serum lipid levels in apoE-deficient mice. Stereological analysis of the immunohistochemical staining revealed that atorvastatin reduced endothelial expression of ICAM-1 and VCAM-1 only in C57BL/6J mice on chow diet.

Conclusion: We have demonstrated that endothelial expression of both VCAM-1 and ICAM-1 does not correlate with cholesterol levels in these mice. Moreover, we showed that 8-week administration of atorvastatin decrease endothelial expression of VCAM-1 and ICAM-1 in C57BL/6J wild type mice beyond its lipid lowering effect but not in C57BL/6J wild type mice fed by atherogenic diet or in apoE-deficient mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Atorvastatin
  • Biomarkers / metabolism
  • Diet, Atherogenic
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Heptanoic Acids / pharmacology*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lipid Metabolism / drug effects*
  • Lipoproteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pyrroles / pharmacology*
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Apolipoproteins E
  • Biomarkers
  • Heptanoic Acids
  • Lipoproteins
  • Pyrroles
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Atorvastatin