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


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.
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Huan
H
Wang
Weiyu
W
Zhang
Rong
R
Tang
Robert P
RP
Hebbel
M Anna
MA
Kowalska
Chunxiang
C
Zhang
Jamey D
JD
Marth
Minoru
M
Fukuda
Chuhong
C
Zhu
Yuqing
Y
Huo
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000503:physiopathology; D023903:Coronary Restenosis / Q000201:enzymology / Q000503:physiopathology; D036904:Leukocyte Rolling / Q000502:physiology; D007962:Leukocytes / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000502:physiology*; D010973:Platelet Adhesiveness; D017539:Tunica Intima / Q000503:physiopathology*
D001057:Apolipoproteins E; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase