Induction of lectin-like oxidized LDL receptor by oxidized LDL and lysophosphatidylcholine in cultured endothelial cells.
A functional change in the endothelium induced by oxidized low density lipoprotein (OxLDL) and its lipid-constituent, lysophosphatidylcholine (LPC), has been implicated in atherogenesis. Recently, we have cloned lectin-like OxLDL receptor (LOX-1) from bovine aortic endothelial cells (BAE). It is the major binding protein for OxLDL on the surface of BAE and is expressed in atheromatous intima of the human carotid artery as well as in intima of normal bovine aorta. In the present study, we found that OxLDL induced the expression of LOX-1 in BAE. OxLDL upregulated the level of mRNA and protein for LOX-1 in a dose- and time-dependent manner. This induction was blocked by anti-LOX-1 antibody. OxLDL also increased the activity for taking up OxLDL in BAE. Similarly, a major constituent of OxLDL, lysophosphatidylcholine (LPC), induced expression of LOX-1 in mRNA, protein and activity level, suggesting the OxLDL induced expression of LOX-1, at least in part, mediated by LPC. Since LPC did not significantly change the half-life of LOX-1 mRNA, the upregulation seemed to occur at the transcriptional level. These results suggest that LOX-1 is upregulated by the uptake of OxLDL through LOX-1 in atheromatous tissues in vivo, which would further enhance the uptake and endothelial activation and dysfunction.
Aoyama
T
T
Department of Pharmacology, Faculty of Medicine, Kyoto, 606, Japan.
Fujiwara
H
H
Masaki
T
T
Sawamura
T
T
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D015854:Up-Regulation
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C495137:OLR1 protein, human; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein