Disease relevance of OLR1

• DNA-protein binding assay with nuclear protein extracts from neuroblastoma cells indicated that the OLR1/3'UTR polymorphism affects the binding of a transcription factor in an allele-dependent manner [1].
• Oxidized LDL receptor gene (OLR1) is associated with the risk of myocardial infarction [2].
• BACKGROUND: We examined the association of 3 polymorphisms in the lectin-like oxidized LDL receptor-1 (LOX1 or OLR1) gene with coronary artery disease in the Women's Ischemia Syndrome Evaluation (WISE) study population [3].
• Articular cartilage specimens from patients with femoral neck fractures were incubated with ox-LDL, with or without preincubation with neutralizing anti-LOX-1 antibody [4].
• METHODS: Human articular cartilage specimens obtained from patients with RA, osteoarthritis (OA), and femoral neck fractures were examined for LOX-1 and ox-LDL by confocal fluorescence microscopy [4].

Psychiatry related information on OLR1

• Investigation of oxidized LDL-receptor 1 (OLR1) as the candidate gene for Alzheimer's disease on chromosome 12 [1].

High impact information on OLR1

• Here we report the molecular cloning, using expression cloning strategy, of an Ox-LDL receptor from vascular endothelial cells [5].
• Here, we report that scavenger receptors are the main HSP binding structures on human dendritic cells and identify LOX-1 as one of these molecules [6].
• Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation [6].
• In situ hybridization showed that Lox1 class transcripts accumulated in the apical and subapical regions of the newly formed tuber, specifically in the vascular tissue of the perimedullary region, the site of the most active cell growth during tuber enlargement [7].
• These observations indicate the following: (1) HCAECs possess abundant LOX-1 as well as Ang II (AT1>AT2) receptors, (2) Ang II upregulates LOX-1 receptor and ox-LDL uptake, (3) the effects of Ang II are mediated by AT1 activation, and (4) Ang II enhances ox-LDL-mediated injury to HCAECs [8].

Chemical compound and disease context of OLR1

• The switch of the predominant class of histamine receptors between H1 and H2 would modulate the effects of histamine on LOX-1 gene expression in monocytes and macrophages, and therefore, would play a certain role in the inflammatory aspects of atherogenesis [9].
• These results suggest that the ACE inhibitor quinapril may have cardioprotective effects in this model of hypertension mediated at least in part through effects on the bradykinin-eNOS and oxidative stress-LOX-1 pathway [10].
• This in vivo inhibition of LOX-1 might be one mechanism for the lipid core reducing effect of pravastatin in atherogenesis [11].

Biological context of OLR1

• Our data suggest that genetic variation in the OLR1 gene may modify the risk of AD in an APOE*4-dependent fashion [1].
• We screened all exons and intron-exon boundaries of the OLR1 gene for new mutations and identified three novel sequence variations in intron 4, intron 5, and the 3' untranslated region (UTR) [1].
• OLR1 is a good candidate gene, due to its function in lipid metabolism pathways, other components of which have been previously implicated as risk factors for AD [12].
• Macrophages from subjects carrying the "non-risk" disease haplotype at OLR1 gene have an increased expression of LOXIN at mRNA and protein level, which results in a significant reduction of apoptosis in response to oxLDL [13].
• Association of single nucleotide polymorphisms in the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction [14].

Anatomical context of OLR1

• Finally, we assessed the impact of these polymorphisms on the level of OLR1 expression in lymphocytes from AD cases compared with controls [15].
• RESULTS: The majority of the RA chondrocytes stained positively with both anti-LOX-1 and anti-ox-LDL antibodies; however, no positive cells were found in OA and normal cartilage specimens [4].
• CLEC-1 is found to be not only expressed in dendritic cells, but also in endothelial cells and in the latter aspect resembles the LOX-1 gene [16].
• Histamine as well as forskolin and dibutyryl cyclic AMP (Bt2-cAMP) stimulated the THP-1 monocytes to express the LOX-1 gene at the transcription level [9].
• We investigated the effect of histamine on the expression of LOX-1 in cells of the human monocytic leukemia cell line THP-1 [9].

Associations of OLR1 with chemical compounds

• In addition, we studied the effect of Ang II on LOX-1 gene and protein expression [8].
• Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation [8].
• Overall, these results demonstrate that high glucose induces endothelial LOX-1 expression [17].
• Linoleic acid increases lectin-like oxidized LDL receptor-1 (LOX-1) expression in human aortic endothelial cells [18].
• LOX-1 staining colocalized with hypochlorite-modified epitopes in the media of injured arteries [19].

Physical interactions of OLR1

• Taking all of the above findings together, ox-HDL activates NF-kappa B via binding to LOX-1 on the cell surface, followed by enhancement of intracellular ROS production in endothelial cells [20].
• Together, cilostazol suppresses RLP-stimulated increased monocyte adhesion to HUVECs by suppression of LOX-1 receptor-coupled NF-kappaB-dependent nuclear transcription via mediation of the maxi-K channel opening [21].

Enzymatic interactions of OLR1

• Lectin-like oxidized LDL receptor-1 (LOX-1) is an oxidized LDL receptor, and its role in restenosis after angioplasty remains unknown [22].
• In this study, we analyzed the effect of endothelin-1 (ET-1) on expression of the lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 LOX-1 and on oxLDL uptake in primary cultures of human umbilical vein endothelial cells (HUVEC) [23].

Regulatory relationships of OLR1

• Anti-LOX-1 antibody reversed ox-LDL-stimulated MMP-3 synthesis to control levels [4].
• The alteration of the responsiveness of LOX-1 expression to histamine was related to suppressed expression of the H2 receptor in THP-1 macrophages [9].
• Whether CRP may regulate endothelial LOX-1 and induce endothelial dysfunction through this receptor is unknown [24].
• In hypertensive animals, not only antihypertensive drugs but also antioxidant agents suppress the LOX-1 overexpression [25].
• The effects of ox-LDL, but not TNFalpha, on MGP and BMP2 expression were inhibited by pretreatment of cells with an antibody directed at LOX-1, a lectin-like receptor for ox-LDL (10 microg/mL) [26].

Other interactions of OLR1

• CONCLUSION: Ox-LDL, principally mediated by LOX-1, enhanced MMP-3 production in articular chondrocytes [4].
• Whereas recombinant full-length DECTIN-1 and LOX-1 are transported to the cell surface, CLEC-1 proteins accumulate in perinuclear compartments [16].
• Because of its close proximity to the A2M gene and because it is abundantly expressed in the brain, we reasoned that the oxidized LDL-receptor 1 (OLR1) gene could be a candidate gene for AD [1].
• Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells [9].
• However, Abeta(40), Abeta(42), Abeta total, and Tau loads or the level of microglial cell activation were not modulated by the 3'-UTR OLR1 polymorphisms [15].

Analytical, diagnostic and therapeutic context of OLR1

• Using quantitative real-time PCR and minigene approach, we show that intronic SNPs, linked to MI, regulate the expression of a new functional splicing isoform of the OLR1 gene, LOXIN, which lacks exon 5 [13].
• The association between ox-LDL and LOX-1 was evaluated by immunofluorescence analysis [4].
• Incubation of HCAECs with Ang II markedly increased LOX-1 mRNA (RT-PCR) and protein (Western blot) expression [8].
• Electrophoretic mobility shift assay data demonstrated that high glucose enhanced, in HAECs, the nuclear protein binding to the NF-kappaB regulatory element of the LOX-1 gene [17].
• Immunosuppression with CyA had no protective effect on vascular injury and LOX-1 expression [19].

References