Along these lines, Keul et al. recently demonstrated that pharmacological inhibition of the S1P-degrading enzyme S1P lyase with 4-deoxypyridoxine (DOP), for a period of up to 12 weeks, accelerated the development of atherosclerosis and resulted in a predominantly unstable plaque phenotype and frequent plaque ruptures with atherothrombosis in an animal model of cholesterol-fed ApoE−/− mice [226]. This evidence concerns the gene APOE and atherosclerosis.