Atorvastatin has distinct effects on endothelial markers in different mouse models of atherosclerosis.
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.
Nachtigal
Petr
P
Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec, Czech Republic. nachti@faf.cuni.cz
Jamborova
Gabriela
G
Pospisilova
Nada
N
Pospechova
Katerina
K
Solichova
Dagmar
D
Zdansky
Petr
P
Semecky
Vladimir
V
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*
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