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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:783.)
© 2003 American Heart Association, Inc.

Vascular Biology

E-Selectin Polymorphism Associated With Myocardial Infarction Causes Enhanced Leukocyte-Endothelial Interactions Under Flow Conditions

Masayuki Yoshida; Yoshio Takano; Taishi Sasaoka; Toru Izumi; Akinori Kimura

From the Department of Vascular Medicine and Medical Biochemistry (M.Y., Y.T.), Graduate School of Medicine, Tokyo Medical and Dental University; Department of Cardiology (T.S., T.I.), Kitasato University School of Medicine; and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

Correspondence to Masayuki Yoshida, MD, 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. E-mail masa.vasc{at}tmd.ac.jp

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.

Methods and 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.

Key Words: E-selectin • polymorphism • endothelium • leukocyte adhesion • mitogen-activated protein kinase

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