Core2 1-6-N-glucosaminyltransferase-i is crucial for the formation of atherosclerotic lesions in apolipoprotein E-deficient mice

Objective - Core2 1-6-N-glucosaminyltransferase-I (C2G1cNAcT-I) modification of adhesion molecules is required for optimal binding to target ligands. The objective of this study was to determine the role of C2G1cNAcT-I in the recruitment of Ly-6C^hi monocytes to atherosclerotic lesions and in lesion formation in mice. Methods and Results - In a whole-blood binding assay, Ly-6C^hi monocytes and certain lymphocytes and natural killer cells from wild-type mice bound to P- and E-selectin. C2G1cNAcT-I deficiency abrogated leukocyte binding to P- and E-selectin in this assay as well as in an in vitro flow chamber assay. Moreover, C2G1cNAcT-I deficiency decreased Ly-6C^hi monocyte interactions with atherosclerotic arteries under physiological flow conditions and also inhibited monocyte recruitment to the peritoneal cavity in mice challenged with thioglycollate. In apolipoprotein E-deficient (apoE^-/-) mice, lack of C2G1cNAcT-I resulted in fewer and smaller atherosclerotic lesions in mouse aortas. Atherosclerosis was also suppressed in C2G1cNAcT-I^-/-/apoE^-/- chimeric mice transplanted with C2G1cNAcT-I^+/+ bone marrow cells. Conclusions - C2G1cNAcT-I in both leukocytes and blood vessel wall cells contributes to leukocyte recruitment to the arterial wall. C2G1cNAcT-I deficiency leads to the formation of small, macrophage-poor, and collagen-rich atherosclerotic lesions.