OLR1

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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][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]

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 sheer stress, and other atherosclerotic stimuli substantially increase LOX-1 expression.[4][6]

LOX-1 may be involved in the regulation of Fas-induced apoptosis. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding.[3] Other ligands for LOX-1 include oxidized high-density lipoprotein, advanced glycation end-products, platelets, and apoptotic cells.[3][6] The binding of platelets to LOX-1 causes a release of vasoconstrictive endothelin, which induces endothelial dysfunction.[6]

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]

Mutations of the OLR1 gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease.[2] 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.

References

  1. 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. PMID 9763655.
  2. 2.0 2.1 2.2 "Entrez Gene: OLR1 oxidized low density lipoprotein (lectin-like) receptor 1".
  3. 3.0 3.1 3.2 Pirillo A, Norata GD, Catapano AL (2013). "LOX-1, OxLDL, and atherosclerosis". Mediators of Inflammation. 2013: 152786. doi:10.1155/2013/152786. PMC 3723318. PMID 23935243.
  4. 4.0 4.1 4.2 Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P (2013). "LOX-1 in atherosclerosis: biological functions and pharmacological modifiers". Cellular and Molecular Life Sciences. 70 (16): 2859–2872. doi:10.1007/s00018-012-1194-z. PMC 4142049. PMID 23124189.
  5. 5.0 5.1 Zmysłowski A, Szterk A (2017). "Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols". Lipids in Health and Disease. 16 (1): 188. doi:10.1186/s12944-017-0579-2. PMC 5625595. PMID 28969682.
  6. 6.0 6.1 6.2 Kakutani M, Masaki T, Sawamura T (2000). "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (1): 360–364. doi:10.1016/j.biochi.2016.10.010. PMC 26668. PMID 10618423.
  7. 7.0 7.1 Brites F, Martin M, Guillas I, Kontush A (2017). "Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit". BBA Clinical. 8: 66–77. doi:10.1016/j.bbacli.2017.07.002. PMC 5597817. PMID 28936395.
  8. 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. PMID 21061468.

Further reading


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