OLR1 explained

Oxidized low-density lipoprotein receptor 1 (Ox-LDL receptor 1) also known as lectin-type oxidized LDL receptor 1 (LOX-1) is a protein that in humans is encoded by the OLR1 gene.^[1]

LOX-1 is the main receptor for oxidized LDL on endothelial cells, macrophages, smooth muscle cells,^[2] and other cell types.^[3] But minimally oxidized LDL is more readily recognized by the TLR4 receptor, and highly oxidized LDL is more readily recognized by the CD36 receptor.^[4]

Function

LOX-1 is a receptor protein which belongs to the C-type lectin superfamily. Its gene is regulated through the cyclic AMP signaling pathway. The protein binds, internalizes and degrades oxidized low-density lipoprotein.

Normally, LOX-1 expression on endothelial cells is low, but tumor necrosis factor alpha, oxidized LDL, blood vessel shear stress, and other atherosclerotic stimuli substantially increase LOX-1 expression.^[5]

LOX-1 may be involved in the regulation of Fas-induced apoptosis. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding. Other ligands for LOX-1 include oxidized high-density lipoprotein, advanced glycation end-products, platelets, and apoptotic cells.^[5] The binding of platelets to LOX-1 causes a release of vasoconstrictive endothelin, which induces endothelial dysfunction.^[5]

This protein may play a role as a scavenger receptor.

Clinical significance

Binding of oxidized LDL to LOX-1 activates NF-κB, leading to monocyte adhesion to enthothelial cells (a pre-requisite for the macrophage foam cell formation of atherosclerosis). Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.^[6] LDL oxidation occurs in the sub-endothelial space, rather than in the circulation. But oxidized cholesterol from foods cooked at high temperature can also be a source of oxysterols.

Mutations of the OLR1 gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease.^[7] When applied to human macrophage-derived foam cells in vitro, the dietary supplement berberine inhibits the expression of the ORL1 gene in response to oxidized low-density lipoprotein cholesterol,^[8] but this has not yet been demonstrated in a living animal or human.

Further reading

• Sawamura T . [Molecular identification of LOX-1 and analysis of its pathophysiological role] . Nippon Yakurigaku Zasshi . 119 . 3 . 145–54 . 2002 . 11915516 . 10.1254/fpj.119.145 . free .
• Mehta JL, Li D . Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor . J. Am. Coll. Cardiol. . 39 . 9 . 1429–35 . 2002 . 11985903 . 10.1016/S0735-1097(02)01803-X . free .
• Sawamura T . [LOX-1: the oxidized LDL receptor expressed in vascular endothelial cells] . Seikagaku . 74 . 5 . 365–76 . 2002 . 12073608 .
• Ando K, Fujita T . Role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the development of hypertensive organ damage . Clin. Exp. Nephrol. . 8 . 3 . 178–82 . 2005 . 15480893 . 10.1007/s10157-004-0288-9 . 24851728 .
• Sawamura T, Kume N, Aoyama T, etal . An endothelial receptor for oxidized low-density lipoprotein . Nature . 386 . 6620 . 73–7 . 1997 . 9052782 . 10.1038/386073a0 . 1997Natur.386...73S . 4321933 .
• Yoshida H, Kondratenko N, Green S, etal . Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor . Biochem. J. . 334 (Pt 1) . Pt 1. 9–13 . 1998 . 9693095 . 10.1042/bj3340009. 1219654 .
• Mehta JL, Li DY . Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells . Biochem. Biophys. Res. Commun. . 248 . 3 . 511–4 . 1998 . 9703956 . 10.1006/bbrc.1998.9004 .
• Yamanaka S, Zhang XY, Miura K, etal . The human gene encoding the lectin-type oxidized LDL receptor (OLR1) is a novel member of the natural killer gene complex with a unique expression profile . Genomics . 54 . 2 . 191–9 . 1999 . 9828121 . 10.1006/geno.1998.5561 .
• Nagase M, Abe J, Takahashi K, etal . Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene . J. Biol. Chem. . 273 . 50 . 33702–7 . 1999 . 9837956 . 10.1074/jbc.273.50.33702 . free.
• Draude G, Hrboticky N, Lorenz RL . The expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) on human vascular smooth muscle cells and monocytes and its down-regulation by lovastatin . Biochem. Pharmacol. . 57 . 4 . 383–6 . 1999 . 9933026 . 10.1016/S0006-2952(98)00313-X .
• Aoyama T, Sawamura T, Furutani Y, etal . Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene . Biochem. J. . 339 (Pt 1) . Pt 1. 177–84 . 1999 . 10085242 . 10.1042/0264-6021:3390177 . 1220142 .
• Li DY, Zhang YC, Philips MI, etal . 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 . Circ. Res. . 84 . 9 . 1043–9 . 1999 . 10325241 . 10.1161/01.res.84.9.1043. free .
• Kataoka H, Kume N, Miyamoto S, etal . Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions . Circulation . 99 . 24 . 3110–7 . 1999 . 10377073 . 10.1161/01.cir.99.24.3110. free .
• Li D, Saldeen T, Romeo F, Mehta JL . Oxidized LDL upregulates angiotensin II type 1 receptor expression in cultured human coronary artery endothelial cells: the potential role of transcription factor NF-kappaB . Circulation . 102 . 16 . 1970–6 . 2000 . 11034947 . 10.1161/01.cir.102.16.1970. free .
• Bull C, Sobanov Y, Röhrdanz B, etal . The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region . Genes Immun. . 1 . 4 . 280–7 . 2001 . 11196705 . 10.1038/sj.gene.6363678 . 21961232 .
• Shi X, Niimi S, Ohtani T, Machida S . Characterization of residues and sequences of the carbohydrate recognition domain required for cell surface localization and ligand binding of human lectin-like oxidized LDL receptor . J. Cell Sci. . 114 . Pt 7 . 1273–82 . 2001 . 10.1242/jcs.114.7.1273 . 11256994 .
• Chen M, Narumiya S, Masaki T, Sawamura T . Conserved C-terminal residues within the lectin-like domain of LOX-1 are essential for oxidized low-density-lipoprotein binding . Biochem. J. . 355 . Pt 2 . 289–96 . 2001 . 11284714 . 10.1042/0264-6021:3550289 . 1221738 .
• Tanimoto A, Murata Y, Nomaguchi M, etal . Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells . FEBS Lett. . 508 . 3 . 345–9 . 2001 . 11728449 . 10.1016/S0014-5793(01)03073-3 . 7257298 . free .
• Sobanov Y, Bernreiter A, Derdak S, etal . A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex . Eur. J. Immunol. . 31 . 12 . 3493–503 . 2002 . 11745369 . 10.1002/1521-4141(200112)31:12<3493::AID-IMMU3493>3.0.CO;2-9 . 42415487 .

Notes and References

1. Li X, Bouzyk MM, Wang X . Assignment of the human oxidized low-density lipoprotein receptor gene (OLR1) to chromosome 12p13.1→p12.3, and identification of a polymorphic CA-repeat marker in the OLR1 gene . Cytogenet Cell Genet . 82 . 1–2 . 34–6 . Nov 1998 . 9763655 . 10.1159/000015059 . 46772688 .
2. Pirillo A, Norata GD, Catapano AL . LOX-1, OxLDL, and atherosclerosis . Mediators of Inflammation . 2013 . 1–12 . 2013 . 10.1155/2013/152786 . 3723318 . 23935243 . free .
3. Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P . LOX-1 in atherosclerosis: biological functions and pharmacological modifiers . . 70 . 16 . 2859–2872 . 2013 . 10.1007/s00018-012-1194-z . 23124189 . 4142049 .
4. Zmysłowski A, Szterk A . Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols . Lipids in Health and Disease . 16 . 1 . 188 . 2017 . 10.1186/s12944-017-0579-2 . 5625595 . 28969682 . free .
5. Kakutani M, Masaki T, Sawamura T . A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1 . . 97 . 1 . 360–364 . 2000 . 10.1016/j.biochi.2016.10.010 . 26668 . 10618423. 2000PNAS...97..360K .
6. Brites F, Martin M, Guillas I, Kontush A . Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit . . 8 . 66–77 . 2017 . 10.1016/j.bbacli.2017.07.002 . 5597817 . 28936395 .
7. Web site: Entrez Gene: OLR1 oxidized low density lipoprotein (lectin-like) receptor 1.
8. Guan S, Wang B, Li W, Guan J, Fang X. Effects of berberine on expression of LOX-1 and SR-BI in human macrophage-derived foam cells induced by ox-LDL. Am J Chin Med. 2010. 38. 6. 1161–9. 21061468. 10.1142/s0192415x10008548.