Increased expression of lectin-like oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits.
A novel lectin-like 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 non-lesion 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.
Chen
M
M
National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Kakutani
M
M
Minami
M
M
Kataoka
H
H
Kume
N
N
Narumiya
S
S
Kita
T
T
Masaki
T
T
Sawamura
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011973:Receptors, LDL / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D016415:Sequence Alignment; D014162:Transfection
D018076:DNA, Complementary; C495137:OLR1 protein, human; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E