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Oxidized LDL (oxLDL) has been shown to activate the sphingomyelinase pathway producing ceramide in vascular smooth muscle cells. Therefore ceramide, which is a biologically active lipid causing apoptosis in a variety of cells, may be involved in the apoptotic action of oxLDL. In this study, we examined whether cholesterol enriched diets affected ceramide metabolism and oxidation product of LDL, represented by degradation of apolipoprotein B-100 (apoB) in apoE-deficient (apoE-/-) mice. ApoE-/- and wild type mice were fed a standard (AIN-76) diet or 1% cholesterol-enriched diet for 8 weeks. Tissue ceramide levels were analyzed using electrospray tandem mass spectrometry (LC-MS/MS). Ceramide levels in the plasma and the liver of apoE-/- mice were intrinsically higher than those of the wild type. In apoE-/- mice, dietary cholesterol significantly increased several ceramides and degradation products of apoB in plasma compared to those fed the control diet. Dietary cholesterol did not affect tissue ceramide levels in the wild type mice. Based on these results, plasma ceramides possibly correlate with the increase in LDL oxidation and are a risk factor for atherosclerosis.