title: Increased protein O-GlcNAc modification inhibits inflammatory and neointimal responses to acute endoluminal arterial injury.
abstract: Inflammation plays a major role in vascular disease. We have shown that leukocyte infiltration and inflammatory mediator expression contribute to vascular remodeling after endoluminal injury. This study tested whether increasing protein O-linked-N-acetylglucosamine (O-GlcNAc) levels with glucosamine (GlcN) and O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) inhibits acute inflammatory and neointimal responses to endoluminal arterial injury. Ovariectomized rats were treated with a single injection of GlcN (0.3 mg/g ip), PUGNAc (7 nmol/g ip) or vehicle (V) 2 h before balloon injury of the right carotid artery. O-GlcNAc-modified protein levels decreased markedly in injured arteries of V-treated rats at 30 min, 2 h, and 24 h after injury but returned to control (contralateral uninjured) levels after 14 days. Both GlcN and PUGNAc increased O-GlcNAc-modified protein levels in injured arteries compared with V controls at 30 min postinjury; the GlcN-mediated increase persisted at 24 h but was not evident at 14 days. Proinflammatory mediator expression increased markedly after injury and was reduced significantly (30-50%) by GlcN and PUGNAc. GlcN and PUGNAc also inhibited infiltration of neutrophils and monocytes in injured arteries. Chronic (14 days) treatment with GlcN reduced neointima formation in injured arteries by 50% compared with V controls. Acute GlcN and PUGNAc treatment increases O-GlcNAc-modified protein levels and inhibits acute inflammatory responses in balloon-injured rat carotid arteries; 14 day GlcN treatment inhibits neointima formation in these vessels. Augmenting O-GlcNAc modification of proteins in the vasculature may represent a novel anti-inflammatory and vasoprotective mechanism.
authors.affiliation: Department of Medicine, Univ. of Alabama at Birmingham, Birmingham, Alabama 35294, USA. dqxing@uab.edu
authors.forename: Dongqi
authors.initials: D
authors.lastname: Xing
authors.forename: Wenguang
authors.initials: W
authors.lastname: Feng
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Nöt
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Miller
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
authors.forename: Erum
authors.initials: E
authors.lastname: Majid-Hassan
authors.forename: John C
authors.initials: JC
authors.lastname: Chatham
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005944:Glucosamine / Q000494:pharmacology*; D006031:Glycosylation; D018836:Inflammation Mediators / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D010052:Ovariectomy; D010091:Oximes / Q000494:pharmacology*; D048448:Phenylcarbamates / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D010091:Oximes; D048448:Phenylcarbamates; C068836:N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)oxime; D005944:Glucosamine; D000117:Acetylglucosamine