Specifically, lowering S1P concentrations through inhibition of sphingosine kinase 1 was reported to enhance high cholesterol diet-induced atherosclerosis in Ldlr KO mice [23] while raising S1P levels through inactivation of S1P lyase in BM-derived cells of Ldlr KO mice reduced HF diet-induced atherosclerosis [22]. This evidence concerns the gene LDLR and atherosclerosis.