title: E-selectin polymorphism associated with myocardial infarction causes enhanced leukocyte-endothelial interactions under flow conditions.
abstract: OBJECTIVE
  Polymorphisms found in genes encoding adhesion molecules have been reported to be associated with atherosclerosis. We investigated the Ser128Arg polymorphism in the E-selectin gene in Japanese patients with myocardial infarction and its functional significance.
  
  
  RESULTS
  Results from 135 patients with myocardial infarction and 327 control subjects revealed that the frequency of Arg128-positive was significantly higher in the patients than in controls (12.6% versus 6.7%; odds ratio, 2.0; 95% CI, 1.04 to 3.85), indicating that the Ser128Arg polymorphism was associated with myocardial infarction. We then generated a recombinant E-selectin adenovirus carrying a mutation (AdS128R-E) and compared it with its wild-type counterpart by evaluating the adhesion characteristics of transduced human umbilical vein endothelial cells under flow. AdS128R-E-transduced human umbilical vein endothelial cells supported significantly more rolling and adhesion of neutrophils and mononuclear cells compared with human umbilical vein endothelial cells transduced with AdWT-E (P<0.001) and also exhibited significantly greater levels of phosphorylation of extracellular signal regulated kinase 1 and 2 and p38 mitogen-activated protein kinase, suggesting that an altered endothelial signaling pathway is associated with this polymorphism.
  
  
  CONCLUSIONS
  Our results suggest that the E-selectin Ser128Arg polymorphism can functionally alter leukocyte-endothelial interactions as well as biochemical and biological consequences, which may account for the pathogenesis of myocardial infarction.
authors.affiliation: Department of Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima Bldg D-256, Bunkyo-ku, Tokyo 113-8519, Japan. masa.vasc@tmd.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takano
authors.forename: Taishi
authors.initials: T
authors.lastname: Sasaoka
authors.forename: Toru
authors.initials: T
authors.lastname: Izumi
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002448:Cell Adhesion; D002478:Cells, Cultured / Q000166:cytology; D002634:Chemotaxis, Leukocyte; D019040:E-Selectin / Q000235:genetics*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D020125:Mutation, Missense; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D009504:Neutrophils / Q000166:cytology; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012212:Rheology; D014161:Transduction, Genetic; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D019040:E-Selectin; D011993:Recombinant Fusion Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases