Disease relevance of Olr1

• OBJECTIVES: The goal of this study was to determine the role of lectin-like oxidized low-density lipoprotein receptors (LOX-1), a recently identified oxidized low-density lipoprotein (ox-LDL) receptor, in ischemia-reperfusion injury to the heart [1].
• Importantly, the LOX-1 antibody reduced apoptosis by 48%, lipid peroxidation by 39%, and myocardial infarct size by 45%, and improved left ventricular function (first derivative of pressure measured over time: -47% to -18%, p < 0.01) [1].
• RESULTS: Ischemia-reperfusion was associated with an increase in LOX-1 expression, lipid peroxidation and apoptosis, a large infarct area, and a decrease in left ventricular function (all, p < 0.01 vs. sham control and ischemia alone groups) [1].
• Both dyslipidemia and RAS activation enhance the expression of a newly described receptor for oxidized-low density lipoprotein (ox-LDL), lectin-like ox-LDL receptor-1 (LOX-1) [2].
• We postulated that the blockade of dyslipidemia with rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor and RAS with candesartan, an angiotensin II type 1 receptor blocker, would have a synergistic inhibitory effect on LOX-1 expression and atherogenesis [2].

High impact information on Olr1

• Recognition of oxidatively damaged and apoptotic cells by an oxidized low density lipoprotein receptor on mouse peritoneal macrophages: role of membrane phosphatidylserine [3].
• In addition, the expression of additional pattern recognition receptors, including TLR9, pentraxin-3, and lectin-like oxidized LDL receptor-1, was regulated, in part, via a MyD88-dependent manner as demonstrated by the attenuated expression of these receptors in MyD88 KO microglia [4].
• We also showed that CD36, a class B scavenger receptor and an oxLDL receptor, promotes H(2)O(2) secretion by macrophages adherent to oxLDL-coated surfaces [5].
• Lectin-like oxidized low-density lipoprotein receptor 1 mediates leukocyte infiltration and articular cartilage destruction in rat zymosan-induced arthritis [6].
• RESULTS: Immunohistochemical study of ZIA demonstrated LOX-1 expression on synovial endothelium and postcapillary venules at 6 hours after the induction of inflammation, with maximum expression detected at 24 hours [6].

Chemical compound and disease context of Olr1

• Cross-talk between dyslipidemia and renin-angiotensin system and the role of LOX-1 and MAPK in atherogenesis studies with the combined use of rosuvastatin and candesartan [2].

Biological context of Olr1

• To further explore the relationship between the structure and function of LOX-1, a mutagenesis study was carried out [7].
• The results indicate that alloimmune responses induce up-regulation of LOX-1 mRNA in transplanted hearts [8].
• Lectin-like oxidized low-density-lipoprotein (oxLDL) receptor-1 (LOX-1) is a cell-surface endocytosis receptor for atherogenic oxLDL, which is highly expressed in endothelial cells [9].
• There was evidence of intense oxidative stress (nitrotyrosine staining), inflammation (CD68 staining), and expression of adhesion molecules and the ox-LDL receptor LOX-1 (gene array analysis) in the atherosclerotic tissues [10].
• CONCLUSIONS: Our findings suggest that histone acetylation could play some role in atherogenesis by modulating expressions of oxLDL receptor and some proatherogenic genes [11].

Anatomical context of Olr1

• BACKGROUND: We hypothesized that atherosclerosis inhibits NO-mediated endothelium-dependent dilation of coronary arterioles through interaction of ox-LDL with its receptor, LOX-1, through the production of O2ÿ- in endothelial cells [12].
• CONCLUSION: LOX-1 induction in arthritic joints might play a role in promoting joint inflammation and cartilage destruction by mediating leukocyte infiltration into the arthritic joints of ZIA rats [6].
• These data imply that lipoproteins can further contribute to foam cell development in atherosclerosis by up-regulating a major OxLDL receptor [13].
• Ox-LDL, a ligand of LOX-1, was also detected in articular chondrocytes [6].
• LOX-1 was also expressed weakly on both joint cartilage and synovium [6].

Associations of Olr1 with chemical compounds

• CONCLUSIONS: These results suggest that ox-LDL impairs endothelium-dependent NO-mediated dilation of coronary arterioles by activation of a signaling cascade involving LOX-1 and NAD(P)H oxidase expression [12].
• This was strong evidence for the involvement of all six Cys in the intrachain disulfide bonds required for proper folding, processing and transport of LOX-1 [7].
• Administration of anti-LOX-1 antibody, which blocks LOX-1 activity, suppressed joint swelling (by 33.5%), leukocyte infiltration, and joint nitrite accumulation at 24 hours, as well as cartilage destruction at 7 days, compared with control rats [6].
• While rosuvastatin and candesartan each had a small inhibitory effect on the expression of LOX-1 in the atherosclerotic tissues, the combination totally blocked the up-regulation of LOX-1 [2].
• By means of glycyrrhizin (GL)-affinity column chromatography, a GL-binding lipoxygenase (gbLOX) was selectively purified from the partially purified soybean LOX-1 fraction [14].

Analytical, diagnostic and therapeutic context of Olr1

• We cloned mouse LOX-1 cDNA to take advantage of a gene-targeting technique to clarify the role of LOX-1 in vivo [15].
• LOX-1 mRNA expression was measured by RT-PCR [8].
• Marked increase in LOX-1 mRNA expression was observed only in allografts [8].
• METHODS: LOX-1 expression and ox-LDL accumulation in arthritic joints were detected by immunohistochemistry using specific mouse anti-LOX-1 and anti-ox-LDL monoclonal antibodies, respectively [6].
• Increased expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the receptor for OxLDL in endothelial cells, has been demonstrated in the atherosclerotic plaques from experimental atherosclerotic animal models and human clinical samples [16].

References