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

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.