title: Atorvastatin has distinct effects on endothelial markers in different mouse models of atherosclerosis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec, Czech Republic. nachti@faf.cuni.cz
authors.forename: Petr
authors.initials: P
authors.lastname: Nachtigal
authors.forename: Gabriela
authors.initials: G
authors.lastname: Jamborova
authors.forename: Nada
authors.initials: N
authors.lastname: Pospisilova
authors.forename: Katerina
authors.initials: K
authors.lastname: Pospechova
authors.forename: Dagmar
authors.initials: D
authors.lastname: Solichova
authors.forename: Petr
authors.initials: P
authors.lastname: Zdansky
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semecky
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D000069059:Atorvastatin; D015415:Biomarkers / Q000378:metabolism; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011758:Pyrroles / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D006538:Heptanoic Acids; D008074:Lipoproteins; D011758:Pyrroles; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000069059:Atorvastatin