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

A novel lectinlike oxidized low density lipoprotein receptor-1 (LOX-1) was recently identified in bovine aortic endothelial cells. It is strongly sugg ested to have a potential role in the initiation and development of atheros clerosis. In this study, we have isolated cDNA clones encoding the rabbit h omologue of LOX-1 by screening a rabbit placenta cDNA library. In amino aci d sequence and domain structure organization, the rabbit LOX-1 is highly co nserved with the human counterpart. Transfection of rabbit LOX-1 cDNA to HE K-293 cells confers on them the activity to bind and internalize oxidized l ow density lipoprotein. Rabbit LOX-1 was identified as a 45-kDa protein by Western blot analysis with a specific monoclonal antibody. Notably, analyse s by reverse transcription-polymerase chain reaction and Western blot revea led that LOX-I was accumulated in 8-week-old Watanabe heritable hyperlipide mic rabbit aortas compared with normal rabbit aortas. Immunostaining confir med that the augmented expression of LOX-I was primarily localized within t he intima at the earliest stages of atherogenesis. The most prominent stain ing was in the endothelial cells of lesions. Furthermore, the distinctive s taining of LOX-1 was identified in the endothelium of nonlesion areas of Wa tanabe heritable hyperlipidemic rabbit aortas. Taken together, these findin gs support the possibility that LOX-1 might be involved in the initiation o f atherosclerosis.