title: Expression and function of ephrin-B1 and its cognate receptor EphB2 in human atherosclerosis: from an aspect of chemotaxis.
abstract: Although several cytokines and chemokines have been demonstrated to play pivotal roles in the pathophysiological conditions of atherosclerosis, few findings exist regarding the expression and function of cytokine-modulating molecules such as ephrin-Bs and their cognate receptors, EphBs, in human atherosclerosis. Therefore, in the present study, we screened novel genes modulating atherogenesis by cDNA array and quantitatively determined them by real-time RT (reverse transcription)-PCR in human carotid atherosclerotic plaques. Ephrin-B1 and EphB2, key regulators of embryogenesis, were significantly up-regulated in plaques compared with those in adjacent control tissues [ephrin-B1, 0.638+/-0.106 compared with 0.831+/-0.152, or 130% (P<0.05); EphB2, 1.296+/-0.281 compared with 2.233+/-0.506, or 172% (P<0.05)]. Immunohistological analysis demonstrated that both ephrin-B1 and EphB2 were expressed in macrophages and T-lymphocytes in plaques as well as in monocytes, T-lymphocytes and arterial endothelial cells isolated from healthy adults. Interestingly, the extracellular domains of ephrin-B1 and EphB2, the expression of which were both enhanced in stimulated THP-1 cells, significantly inhibited spontaneous (22.5 and 27.6% respectively; P<0.01) and MCP-1 (monocyte chemoattractant protein-1)-dependent (29.7 and 22.6% respectively; P<0.01) migration of monocytes. In conclusion, these results demonstrate that ephrin-B1 and EphB2 are overexpressed in atherosclerotic tissue and might locally regulate cell migration, possibly through modulating cytokine-related chemotaxic activity; however, the functional role of these molecules in atherogenesis should be investigated further.
authors: Division of Biotechnology, National Cardiovascular Center, Osaka, Japan.
authors: Aiji
authors: A
authors: Sakamoto
authors: Hatsue
authors: H
authors: Ishibashi-Ueda
authors: Yuka
authors: Y
authors: Sugamoto
authors: Takeo
authors: T
authors: Higashikata
authors: Susumu
authors: S
authors: Miyamoto
authors: Masa-Aki
authors: MA
authors: Kawashiri
authors: Kunimasa
authors: K
authors: Yagi
authors: Tetsuo
authors: T
authors: Konno
authors: Kenshi
authors: K
authors: Hayashi
authors: Noboru
authors: N
authors: Fujino
authors: Hidekazu
authors: H
authors: Ino
authors: Yoshiyu
authors: Y
authors: Takeda
authors: Masakazu
authors: M
authors: Yamagishi
mesh_terms: D002339:Carotid Arteries / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000378:metabolism*; D016022:Case-Control Studies; D002634:Chemotaxis, Leukocyte; D016894:Endarterectomy, Carotid; D042783:Endothelial Cells / Q000378:metabolism; D036387:Ephrin-B1 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D036183:Receptor, EphB2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D036387:Ephrin-B1; D036183:Receptor, EphB2