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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:180.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Core2 1-6-N-Glucosaminyltransferase-I Is Crucial for the Formation of Atherosclerotic Lesions in Apolipoprotein E–Deficient Mice

Huan Wang; Rong Tang; Weiyu Zhang; Karine Amirikian; Zhen Geng; Jianguo Geng; Robert P. Hebbel; Lijun Xia; Jamey D. Marth; Minoru Fukuda; Shigeki Katoh; Yuqing Huo

From the Department of Medicine (H.W., R.T., W.Z., K.A., Z.G., J.G., R.P.H., Y.H.), University of Minnesota, Minneapolis; the Oklahoma Medical Research Foundation (L.X.), Oklahoma City; the Department of Cellular and Molecular Medicine and the Howard Hughes Medical Institute (J.D.M.), University of California San Diego, La Jolla, Calif; the Glycobiology/Carbohydrate Chemistry Program (M.F.), Burnham Institute for Medical Research, La Jolla, Calif; and the Department of Cell Regulation (S.K.), Kagawa University, Kagawa, Japan.

Correspondence to Yuqing Huo, MD, PhD, Cardiovascular Division & Vascular Biology Center, Department of Medicine, University of Minnesota, 420 Delaware St SE, MMC508, Minneapolis, MN 55455. E-mail Yuqing{at}umn.edu

Objective— Core2 1-6-N-glucosaminyltransferase-I (C2GlcNAcT-I) modification of adhesion molecules is required for optimal binding to target ligands. The objective of this study was to determine the role of C2GlcNAcT-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. C2GlcNAcT-I deficiency abrogated leukocyte binding to P- and E-selectin in this assay as well as in an in vitro flow chamber assay. Moreover, C2GlcNAcT-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 C2GlcNAcT-I resulted in fewer and smaller atherosclerotic lesions in mouse aortas. Atherosclerosis was also suppressed in C2GlcNAcT-I^–/–/apoE^–/– chimeric mice transplanted with C2GlcNAcT-I^+/+ bone marrow cells.

Conclusions— C2GlcNAcT-I in both leukocytes and blood vessel wall cells contributes to leukocyte recruitment to the arterial wall. C2GlcNAcT-I deficiency leads to the formation of small, macrophage-poor, and collagen-rich atherosclerotic lesions.

Key Words: monocyte • adhesion molecule • atherosclerosis

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