A hallmark feature of
atherosclerosis is that circulating mononuclear cells adhere to the endothelium and migrate into the subendothelial space. This adhesion is mediated by molecules such as
selectins that are expressed on the surfaces of both leukocytes and endothelial cells. In this study, we have determined the role of tissue-specific
fucosyltransferase VII (FucT-VII), an
enzyme necessary for
selectin ligand synthesis, in the development of
atherosclerosis. We adopted a scheme of transplanting either FucT-VII(-/-)GFP(+) bone marrow into lethally irradiated
low-density lipoprotein receptor low density lipoprotein receptor mice or FucT-VII(+/+) GFP(+) bone marrow into FucT-VII(-/-),
low density lipoprotein receptor double-mutant mice to evaluate the roles of E- and
P-selectin ligands versus
L-selectin ligands, respectively, in diet-induced
atherosclerosis. GFP was used to track the transplanted cells. Our results indicate that, compared with controls, selective disruption of E- and
P-selectin ligand synthesis resulted in a significant reduction in
atherosclerosis. Selective disruption of
L-selectin ligand production did not reduce
atherosclerosis as robustly as disruption of E- and
P-selectin ligands. In both groups, however, there was a significant reduction in the accumulation of macrophages in the lesion. These studies indicate that
selectin ligands, particularly those for E- and P-
selectins, play an important role in the pathogenesis of
atherosclerosis by regulating macrophage accumulation in atherosclerotic lesions.