Atorvastatin therapy (20 mg / day given for 2 months) to hypercholesterolemic patients resulted in a reduction, by 59%, in their human monocyte-derived macrophages (HMDM) cholesterol content. The macrophage lipid peroxides content, and cell-mediated oxidation of LDL were reduced by 25% and 48% after atorvastatin therapy, as compared to the patients macrophages before therapy. This therapy increased paraoxonases 2 (PON2) mRNA expression and activity by 76% and 200%, respectively. Similar results were obtained upon adding atorvastatin to macrophages in vitro. By adding acetylated-LDL or atorvastatin in the presence of mevalonate to macrophages from control healthy subject we were able to demonstrate that macrophage cholesterol content determines the extent of PON2 expression. The increased macrophage PON2 expression after atorvastatin therapy can be related to atorvastatin induced reduction in cellular cholesterol content. These beneficial effects of atorvastatin contribute to the attenuation of atherosclerosis development in hypercholesterolemic patients.
Keywords: paraoxonase, oxidative stress, macrophages, cholesterol, atorvastatin
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