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 Citations (Scopus)

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

Fingerprint

Neointima
Apolipoproteins E
Arteries
Regeneration
Platelet Factor 4
Leukocytes
Wounds and Injuries
Blood Platelets
Ligands
Selectins
P-Glycoprotein
beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase
Carotid Arteries
Blood Vessels

Keywords

  • Endothelial recovery
  • Leukocytes
  • Neointima formation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Core2 1-6-N-glucosaminyltransferase-I deficiency protects injured arteries from neointima formation in ApoE-deficient mice. / Wang, Huan; Zhang, Weiyu; Tang, Rong; Hebbel, Robert P.; Kowalska, M. Anna; Zhang, Chunxiang; Marth, Jamey D.; Fukuda, Minoru; Zhu, Chuhong; Huo, Yuqing.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 29, No. 7, 01.07.2009, p. 1053-1059.

Research output: Contribution to journalArticle

Wang, Huan ; Zhang, Weiyu ; Tang, Rong ; Hebbel, Robert P. ; Kowalska, M. Anna ; Zhang, Chunxiang ; Marth, Jamey D. ; Fukuda, Minoru ; Zhu, Chuhong ; Huo, Yuqing. / Core2 1-6-N-glucosaminyltransferase-I deficiency protects injured arteries from neointima formation in ApoE-deficient mice. In: Arteriosclerosis, thrombosis, and vascular biology. 2009 ; Vol. 29, No. 7. pp. 1053-1059.
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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.",
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T1 - Core2 1-6-N-glucosaminyltransferase-I deficiency protects injured arteries from neointima formation in ApoE-deficient mice

AU - Wang, Huan

AU - Zhang, Weiyu

AU - Tang, Rong

AU - Hebbel, Robert P.

AU - Kowalska, M. Anna

AU - Zhang, Chunxiang

AU - Marth, Jamey D.

AU - Fukuda, Minoru

AU - Zhu, Chuhong

AU - Huo, Yuqing

PY - 2009/7/1

Y1 - 2009/7/1

N2 - 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.

AB - 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.

KW - Endothelial recovery

KW - Leukocytes

KW - Neointima formation

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JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

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