Core2 1-6-N-glucosaminyltransferase-I deficiency protects injured arteries from neointima formation in ApoE-deficient mice.

Abstract

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.

• Authors: Huan Wang, Weiyu Zhang, Rong Tang, Robert P Hebbel, M Anna Kowalska, Chunxiang Zhang, Jamey D Marth, Minoru Fukuda, Chuhong Zhu, Yuqing Huo
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 29 Issue 7 Pg. 1053-9 (Jul 2009) ISSN: 1524-4636 [Electronic] United States
• PMID: 19372458 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• N-Acetylglucosaminyltransferases
• beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase

Topics

• Animals
• Apolipoproteins E (deficiency)
• Carotid Artery Diseases (enzymology, physiopathology)
• Coronary Restenosis (enzymology, physiopathology)
• Leukocyte Rolling (physiology)
• Leukocytes (enzymology, physiology)
• Mice
• Mice, Knockout
• N-Acetylglucosaminyltransferases (deficiency, physiology)
• Platelet Adhesiveness
• Tunica Intima (physiopathology)