Interestingly, only pharmacological inhibition of SphK1 with SK1-I or its genetic suppression protected against sortilin-induced endothelial dysfunction and superoxide generation in HUVECs, whereas these effects were not observed after inhibition of SphK2 with either K145 or siRNA-mediated knockdown (Figure 2, E and F, and Supplemental Figure 2, B and C). This evidence concerns the gene SPHK2 and endothelial dysfunction.