Increased expression of lectinlike oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits

被引:167
作者
Chen, MY
Kakutani, M
Minami, M
Kataoka, H
Kume, N
Narumiya, S
Kita, T
Masaki, T
Sawamura, T [1 ]
机构
[1] Natl Cardiovasc Ctr, Res Inst, Suita, Osaka 5658565, Japan
[2] Kyoto Univ, Grad Sch Med, Fac Med, Dept Pharmacol, Kyoto, Japan
[3] Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Kyoto, Japan
[4] Osaka Univ, Grad Sch Pharmaceut Sci, Dept Mol Pathophysiol, Osaka, Japan
关键词
atherosclerosis; endothelium; oxidized low density lipoproteins; lectinlike oxidized low density lipoprotein receptor-1; Watanabe heritable hyperlipidemic rabbits;
D O I
10.1161/01.ATV.20.4.1107
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A novel lectinlike oxidized low density lipoprotein receptor-1 (LOX-1) was recently identified in bovine aortic endothelial cells. It is strongly suggested to have a potential role in the initiation and development of atherosclerosis. In this study, we have isolated cDNA clones encoding the rabbit homologue of LOX-1 by screening a rabbit placenta cDNA library. In amino acid sequence and domain structure organization, the rabbit LOX-1 is highly conserved with the human counterpart. Transfection of rabbit LOX-1 cDNA to HEK-293 cells confers on them the activity to bind and internalize oxidized low density lipoprotein. Rabbit LOX-1 was identified as a 45-kDa protein by Western blot analysis with a specific monoclonal antibody. Notably, analyses by reverse transcription-polymerase chain reaction and Western blot revealed that LOX-I was accumulated in 8-week-old Watanabe heritable hyperlipidemic rabbit aortas compared with normal rabbit aortas. Immunostaining confirmed that the augmented expression of LOX-I was primarily localized within the intima at the earliest stages of atherogenesis. The most prominent staining was in the endothelial cells of lesions. Furthermore, the distinctive staining of LOX-1 was identified in the endothelium of nonlesion areas of Watanabe heritable hyperlipidemic rabbit aortas. Taken together, these findings support the possibility that LOX-1 might be involved in the initiation of atherosclerosis.
引用
收藏
页码:1107 / 1115
页数:9
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