Expression and function of ephrin-B1 and its cognate receptor EphB2 in human atherosclerosis: from an aspect of chemotaxis.
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.
Sakamoto
Aiji
A
Division of Biotechnology, National Cardiovascular Center, Osaka, Japan.
Ishibashi-Ueda
Hatsue
H
Sugamoto
Yuka
Y
Higashikata
Takeo
T
Miyamoto
Susumu
S
Kawashiri
Masa-Aki
MA
Yagi
Kunimasa
K
Konno
Tetsuo
T
Hayashi
Kenshi
K
Fujino
Noboru
N
Ino
Hidekazu
H
Takeda
Yoshiyu
Y
Yamagishi
Masakazu
M
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
D036387:Ephrin-B1; D036183:Receptor, EphB2