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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1053.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Core2 1-6-N-Glucosaminyltransferase-I Deficiency Protects Injured Arteries From Neointima Formation in ApoE-Deficient Mice

Huan Wang; Weiyu Zhang; Rong Tang; Robert P. Hebbel; M. Anna Kowalska; Chunxiang Zhang; Jamey D. Marth; Minoru Fukuda; Chuhong Zhu; Yuqing Huo

From the Department of Medicine (H.W., W.Z., R.T., R.P.H., C.Z., Y.H.), University of Minnesota, Minneapolis; the Department of Hematology (M.A.K.), Children’s Hospital of Philadelphia, Pa; the Department of Anesthesiology (C.Z.), New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark; the Department of Cellular and Molecular Medicine and the Howard Hughes Medical Institute (J.D.M.), University of California San Diego, La Jolla; and Glycobiology/Carbohydrate Chemistry Program (M.F.), Burnham Institute for Medical Research, La Jolla, Calif.

Correspondence to Yuqing Huo, MD, PhD, Cardiovascular Division and Vascular Biology Center, Department of Medicine, University of Minnesota, 420 Delaware St SE, MMC508, Minneapolis, MN 55455. E-mail yuqing{at}umn.edu, or Chuhong Zhu, MD, PhD, Department of Anatomy, Third Medical University, Gao Tan Yan Street, Shaping Ba District, Chongqing, China, 400038. E-mail zhuxx319@umn.edu.

Objective— Core2 1 to 6-N-glucosaminyltransferase-I (C2GlcNAcT-I) plays an important role in optimizing the binding functions of several selectin ligands, including P-selectin glycoprotein ligand. We used apolipoprotein E (ApoE)-deficient atherosclerotic mice to investigate the role of C2GlcNAcT-I in platelet and leukocyte interactions with injured arterial walls, in endothelial regeneration at injured sites, and in the formation of arterial neointima.

Methods and Results— Arterial neointima induced by wire injury was smaller in C2GlcNAcT-I-deficient apoE^–/– mice than in control apoE^–/– mice (a 79% reduction in size). Compared to controls, apoE^–/– mice deficient in C2GlcNAcT-I also demonstrated less leukocyte adhesion on activated platelets in microflow chambers (a 75% reduction), and accumulation of leukocytes at injured areas of mouse carotid arteries was eliminated. Additionally, endothelial regeneration in injured lumenal areas was substantially faster in C2GlcNAcT-I-deficient apoE^–/– mice than in control apoE^–/– mice. Endothelial regeneration was associated with reduced accumulation of platelet factor 4 (PF4) at injured sites. PF4 deficiency accelerated endothelial regeneration and protected mice from neointima formation after arterial injury.

Conclusions— C2GlcNAcT-I deficiency suppresses injury-induced arterial neointima formation, and this effect is attributable to decreased leukocyte recruitment to injured vascular walls and increased endothelial regeneration. Both C2GlcNAcT-I and PF4 are promising targets for the treatment of arterial restenosis.

C2GlcNAcT-I deficiency suppresses injury-induced arterial neointima formation, and this effect is attributable to decreased leukocyte recruitment to injured vascular walls and increased endothelial regeneration.

Key Words: leukocytes • endothelial recovery • neointima formation