© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Increased Expression of Lectinlike Oxidized Low Density Lipoprotein Receptor-1 in Initial Atherosclerotic Lesions of Watanabe Heritable Hyperlipidemic Rabbits
From the National Cardiovascular Center Research Institute (M.C., M.K., T.M., T.S.), Suita, Osaka, Japan; the Department of Pharmacology (M.C., S.N.), Faculty of Medicine, and the Department of Geriatric Medicine (M.M., H.K., N.K., T.K.), Graduate School of Medicine, Kyoto University, Kyoto, Japan; and the Department of Molecular Pathophysiology (T.S.), Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Correspondence to Tatsuya Sawamura, MD, PhD, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan. E-mail sawamura{at}ri.ncvc.go.jp
Abstract—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-1 was accumulated in 8-week-old Watanabe heritable hyperlipidemic rabbit aortas compared with normal rabbit aortas. Immunostaining confirmed that the augmented expression of LOX-1 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.
Key Words: atherosclerosis • endothelium • oxidized low density lipoproteins • lectinlike oxidized low density lipoprotein receptor-1 • Watanabe heritable hyperlipidemic rabbits
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