Increase in secretory sphingomyelinase activity and specific ceramides in the aorta of apolipoprotein E knockout mice during aging.

Atherosclerosis is caused by many factors, one of which is oxidative stress. We recently demonstrated that systemic oxidative stress increased secretory sphingomyelinase (sSMase) activity and generated ceramides in the plasma of diabetic rats. In addition, we also showed that the total ceramide level in human plasma correlated with the level of oxidized low-density lipoprotein. To investigate the relationship between ceramide species and atherogenesis during aging, we compared age-related changes in ceramide metabolism in apolipoprotein E knock out mice (apoE(-/-)) and wild type mice (WT). Although the total plasma ceramide level was higher in apoE(-/-) than that in WT at all ages, it decreased with increasing age. sSMase activity increased at 65 weeks (w) of age in both strains of mice. When apoE(-/-) developed atherosclerosis at 15 w of age, C18:0, C22:0, and C24:0 ceramide levels in the apoE(-/-) aorta significantly increased. Furthermore, at 65 w of age C16:0 and C24:1 ceramide levels were significantly higher than those in WT. These results suggested that elevation in levels of specific ceramide species due to sSMase activity contributed to atherogenesis during aging.