ST6GAL1 negatively regulates monocyte transendothelial migration and atherosclerosis development

Abstract Monocyte transendothelial migration is a critical step in the initial stage of atherosclerosis, in which the involvement of α-2,6 sialyltransferase 1 (ST6GAL1) has been confirmed by increasing evidence. But the direct relationship between ST6GAL1 and atherosclerosis remains incompletely uncertain. In this study, we demonstrated that the expression level of ST6GAL1 in vascular endothelium was significantly decreased in atherosclerosis development process, while obviously recovered after atherosclerosis regression. Further analysis showed that knockdown of ST6GAL1 by RNA interference in vascular endothelial cells EA. hy926 obviously promoted TNFα-triggered monocyte-transendothelial migration, whereas overexpression of ST6GAL1 strongly inhibited monocyte-transendothelial migration. Moreover, we firstly found β-catenin is a sialylated protein and its sialylation level is decreased in TNFα-treated EA. hy926 cells, suggesting that the function of ST6GAL1 in preventing both atherosclerosis development and monocyte transendothelial migration might result from the sialylation of β-catenin of endothelium. Our results suggested ST6GAL1 might be a potential target for atherosclerosis prevention and treatment.