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

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1053-1059
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2009

Keywords

  • Endothelial recovery
  • Leukocytes
  • Neointima formation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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