In agreement with our findings, Keul et al. investigated the effect of persistently high S1P levels on atherosclerosis in cholesterol-fed ApoE−/− mice over 12 weeks and found that high endogenous S1P levels promote atherosclerosis, impair cholesterol efflux, and lead to true plaque rupture (Keul et al., 2022). This evidence concerns the gene APOE and atherosclerosis.