Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells.
Although macrophages scavenge oxidatively modified low density lipoprotein (ox-LDL) via specific receptors, the uptake of ox-LDL by endothelial cells is thought to be mediated by a different receptor (LOX-1). We examined the presence of LOX-1 on cultured human coronary artery endothelial cells (HCAECs) by RT-PCR, radioligand blot, and binding assays. LOX-1 mRNA and protein were consistently identified in HCAECs. [125I]-ox-LDL binding assay also identified high affinity binding sites for LOX-1 on HCAECs (KD: 1.71 x 10(-8) M: Bmax: 29.7 ng/mg protein). There was no change in LOX-1 expression in HCAECs treated with native-LDL. In contrast, incubation of HCAECs with ox-LDL (10-40 micrograms/ml) increased LOX-1 expression (mRNA and protein). The upregulation of LOX-1 expression appeared to be dependent on ox-LDL concentration. Higher concentration (100 micrograms/ml) however, decreased LOX-1 expression, perhaps related to its cytotoxic effect. These observations indicate that ox-LDL upregulates its own receptor on HCAECs. This phenomenon may explain enhanced uptake of ox-LDL by HCAECs in hyperlipidemia resulting in cellular dysfunction.
Department of Medicine, University of Florida, Gainesville, USA. mehta@medmac.ufl.edu
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Mehta
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Li
D002478:Cells, Cultured; D003331:Coronary Vessels; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D014158:Transcription, Genetic / Q000187:drug effects
D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein