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 OLR1gene.[1][2]
LOX-1 is the main receptor for oxidized LDL on endothelial cells, macrophages, smooth muscle cells,[3] and other cell types.[4] But minimally oxidized LDL is more readily recognized by the TLR4 receptor, and highly oxidized LDL is more readily recognized by the CD36 receptor.[5]
This protein may play a role as a scavenger receptor.[2]
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).[4] Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.[7] LDL oxidation occurs in the sub-endothelial space, rather than in the circulation.[7] But oxidized cholesterol from foods cooked at high temperature can also be a source of oxysterols.[5]
↑Li X, Bouzyk MM, Wang X (Nov 1998). "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. doi:10.1159/000015059. PMID9763655.
↑Guan S, Wang B, Li W, Guan J, Fang X (2010). "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. 38 (6): 1161–9. doi:10.1142/s0192415x10008548. PMID21061468.
Further reading
Sawamura T (2002). "[Molecular identification of LOX-1 and analysis of its pathophysiological role]". Nippon Yakurigaku Zasshi. 119 (3): 145–54. doi:10.1254/fpj.119.145. PMID11915516.
Mehta JL, Li D (2002). "Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor". J. Am. Coll. Cardiol. 39 (9): 1429–35. doi:10.1016/S0735-1097(02)01803-X. PMID11985903.
Sawamura T (2002). "[LOX-1: the oxidized LDL receptor expressed in vascular endothelial cells]". Seikagaku. 74 (5): 365–76. PMID12073608.
Ando K, Fujita T (2005). "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. doi:10.1007/s10157-004-0288-9. PMID15480893.
Sawamura T, Kume N, Aoyama T, et al. (1997). "An endothelial receptor for oxidized low-density lipoprotein". Nature. 386 (6620): 73–7. doi:10.1038/386073a0. PMID9052782.
Mehta JL, Li DY (1998). "Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells". Biochem. Biophys. Res. Commun. 248 (3): 511–4. doi:10.1006/bbrc.1998.9004. PMID9703956.
Yamanaka S, Zhang XY, Miura K, et al. (1999). "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. doi:10.1006/geno.1998.5561. PMID9828121.
Nagase M, Abe J, Takahashi K, et al. (1999). "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. doi:10.1074/jbc.273.50.33702. PMID9837956.
Draude G, Hrboticky N, Lorenz RL (1999). "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. doi:10.1016/S0006-2952(98)00313-X. PMID9933026.
Li DY, Zhang YC, Philips MI, et al. (1999). "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. doi:10.1161/01.res.84.9.1043. PMID10325241.
Kataoka H, Kume N, Miyamoto S, et al. (1999). "Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions". Circulation. 99 (24): 3110–7. doi:10.1161/01.cir.99.24.3110. PMID10377073.
Li D, Saldeen T, Romeo F, Mehta JL (2000). "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. doi:10.1161/01.cir.102.16.1970. PMID11034947.
Bull C, Sobanov Y, Röhrdanz B, et al. (2001). "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. doi:10.1038/sj.gene.6363678. PMID11196705.
Shi X, Niimi S, Ohtani T, Machida S (2001). "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. PMID11256994.
Tanimoto A, Murata Y, Nomaguchi M, et al. (2001). "Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells". FEBS Lett. 508 (3): 345–9. doi:10.1016/S0014-5793(01)03073-3. PMID11728449.
Sobanov Y, Bernreiter A, Derdak S, et al. (2002). "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. doi:10.1002/1521-4141(200112)31:12<3493::AID-IMMU3493>3.0.CO;2-9. PMID11745369.