Disease relevance of Oldlr1

• Preadministration of anti-LOX-1 antibody reduced the degree of leukopenia and completely rescued the animals, whereas control IgG did not [1].
• In a model of low-dose endotoxin-induced uveitis, anti-LOX-1 antibody efficiently suppressed leukocyte infiltration and protein exudation [1].
• Here, we report on the role of LOX-1 in intimal hyperplasia, in which proinflammatory and oxidative stimuli are increased [2].
• Quite unexpectedly, the expression was dramatically up-regulated in the aorta in hypertensive SHR-SP/Izm rats compared with very low levels in control WKY/Izm rats, suggesting a potential role for LOX-1 in the pathogenesis of hypertension as well as atherosclerosis [3].
• LOX-1 antibody, but not nonspecific IgG, also reduced myocardial infarct size (P < 0.01 vs. saline-treated I/R group) [4].

High impact information on Oldlr1

• The ability of LOX-1 to capture leukocytes under physiologic shear was confirmed in an in vitro flow model [1].
• Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation [1].
• In situ videomicroscopic analyses of leukocyte interactions with retinal veins revealed that anti-LOX-1 antibody reduced the number of rolling leukocytes and increased the velocity of rolling, suggesting that LOX-1 functions as a vascular tethering ligand [1].
• OBJECTIVE: LOX-1 is a multi-ligand receptor originally identified as the endothelial oxidized LDL receptor [2].
• These findings suggest the importance of LOX-1 expression in the pathogenesis of neointimal formation in conjunction with oxidative stress and leukocyte infiltration [2].

Chemical compound and disease context of Oldlr1

• In Ang II-infused rats SBP, aortic hypertrophy, endothelial dysfunction, LOX-1 expression, aortic O(2)(-) and ONOO(-) production, and plasma free 8-F(2)alpha-isoprostane levels were significantly reduced by amlodipine treatment [5].
• After 1 h ischemia of bilateral kidneys plus 3, 6, or 12 h reperfusion, we first revealed that LOX-1 mRNA expression was increased in renal cortex and medulla at 6 h after reperfusion, which was decreased by L-arginine supplement [6].

Biological context of Oldlr1

• Unique repetitive sequence and unexpected regulation of expression of rat endothelial receptor for oxidized low-density lipoprotein (LOX-1) [3].
• Treatment of rats with the LOX-1 antibody prevented I/R-induced upregulation of LOX-1 and reduced MMP-1 and adhesion molecule expression as well as leukocyte recruitment [4].
• Doxorubicin-induced expression of LOX-1 in H9c2 cardiac muscle cells and its role in apoptosis [7].
• Oxidized LDL dose-dependently reduced chondrocyte viability, inducing non-apoptotic cell death, which was again suppressed by anti-LOX-1 antibody treatment [8].
• Moreover, reduction of blood pressure by the angiotensin II type 1 (AT1) receptor antagonist candesartan significantly suppressed the renal LOX-1 expression, and this suppression was accompanied by amelioration of renal injury [9].

Anatomical context of Oldlr1

• Thus, LOX-1 is an adhesion molecule involved in leukocyte recruitment and may represent an attractive target for modulation of endotoxin-induced inflammation [1].
• LOX-1 expression is also induced in smooth muscle cells in response to proinflammatory and oxidative stimuli [2].
• A recently identified lectin-like oxidized low-density lipoprotein receptor (LOX-1) mediates endothelial cell injury and facilitates inflammatory cell adhesion [4].
• DiI-labeled oxidized LDL was bound and ingested by chondrocytes via LOX-1 [8].
• Up-regulation of LOX-1 is implicated in apoptosis in both vascular smooth muscle cells and in endothelial cells [7].

Associations of Oldlr1 with chemical compounds

• Doxorubicin-induced LOX-1 expression in a concentration- and time-dependent fashion [7].
• In this study, we examined the vascular expression of LOX-1 in streptozotocin-induced diabetic rats [10].
• In cultured aortic endothelial cells, diabetic rat serum and advanced glycation endproducts-BSA induced LOX-1 expression, while control rat serum along with high glucose did not [10].
• The present study provides evidence that HHcy does produce renal oxidative stress mediated by lipid peroxidation, and that the increased kidney MDA displayed by FF animals may enhance kidney antioxidant activity and thereby attenuate both kidney damage and expression of LOX-1 [11].
• However, the molecular mechanisms by which betaxolol, a specific beta 1-antagonist, stimulates endothelial NO synthase (eNOS) expression associated with LOX-1 and VEGF are unclear [12].

Enzymatic interactions of Oldlr1

• We also demonstrated that amlodipine or manidipine prevented the Ang II-induced increase in lectin-like oxidized low-density lipoprotein receptor1 (LOX-1) content, thereby restoring control levels [13].

Regulatory relationships of Oldlr1

• The activity of p38 MAPK was increased during I/R (P < 0.01 vs. sham control), and use of LOX-1 antibody inhibited p38 MAPK activation (P < 0.01) [4].
• METHODS AND RESULTS: In primary cardiac myocytes from neonatal rats, immunohistochemical analyses using a specific monoclonal antibody against LOX-1 demonstrated that LOX-1 expression was markedly induced by stimulation with norepinephrine and endothelin-1 [14].
• Antioxidant catalase also blocked LOX-1-induced apoptosis as well as activation of p38 MAPK [14].

Other interactions of Oldlr1

• These findings indicate that myocardial I/R upregulates LOX-1 expression, which through p38 MAPK activation increases the expression of MMP-1 and adhesion molecules [4].
• LOX-1, the endothelial oxidized LDL receptor might be involved in the pathogenesis of diabetic atherosclerosis [10].
• LOX-1 inhibition in myocardial ischemia-reperfusion injury: modulation of MMP-1 and inflammation [4].
• Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and the opposing effect of L-arginine [6].
• Increased expression of NAD(P)H oxidase p22phox, p47phox, gp91phox and LOX-1 in DS rats were inhibited by Y-27632 [15].

Analytical, diagnostic and therapeutic context of Oldlr1

• Northern-blot analysis revealed that LOX-1 mRNA was expressed predominantly in the lung [3].
• Manipulation of LOX-1 activity is a novel potential therapeutic target to prevent restenosis after angioplasty [2].
• LOX-1 expression was markedly increased during I/R (P < 0.01 vs. sham control group) [4].
• Immunohistochemistry revealed that the most distinctive staining of LOX-1 was in the endothelial cells, especially in the bifurcations of artery branches from aorta [10].
• LOX-1 mRNA and protein expression was assessed by RT-PCR and Western blotting [7].

References