Home LiteratureArticle Details
PMID: 23935243 Published · ppublish English Journal Article Review

LOX-1, OxLDL, and atherosclerosis.

Mediators of inflammation ·Vol. 2013 ·2013-00-00 ·Pages 152786

Pirillo A, Norata GD, Catapano AL

Abstract

Oxidized low-density lipoprotein (OxLDL) contributes to the atherosclerotic plaque formation and progression by several mechanisms, including the induction of endothelial cell activation and dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation. Vascular wall cells express on their surface several scavenger receptors that mediate the cellular effects of OxLDL. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the main OxLDL receptor of endothelial cells, and it is expressed also in macrophages and smooth muscle cells. LOX-1 is almost undetectable under physiological conditions, but it is upregulated following the exposure to several proinflammatory and proatherogenic stimuli and can be detected in animal and human atherosclerotic lesions. The key contribution of LOX-1 to the atherogenic process has been confirmed in animal models; LOX-1 knockout mice exhibit reduced intima thickness and inflammation and increased expression of protective factors; on the contrary, LOX-1 overexpressing mice present an accelerated atherosclerotic lesion formation which is associated with increased inflammation. In humans, LOX-1 gene polymorphisms were associated with increased susceptibility to myocardial infarction. Inhibition of the LOX-1 receptor with chemicals or antisense nucleotides is currently being investigated and represents an emerging approach for controlling OxLDL-LOX-1 mediated proatherogenic effects.

MeSH Terms
Animals Apoptosis Atherosclerosis/genetics,pathology Endothelial Cells/cytology Endothelium, Vascular/pathology Humans Inflammation Ligands Lipoproteins, LDL/metabolism Macrophages/cytology,metabolism Mice Mice, Knockout Myocardial Infarction/pathology Myocytes, Smooth Muscle/cytology Platelet Activation Reperfusion Injury/pathology Scavenger Receptors, Class E/metabolism
Chemicals
Ligands Lipoproteins, LDL OLR1 protein, human Scavenger Receptors, Class E oxidized low density lipoprotein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pirillo Angela
Center for the Study of Atherosclerosis, E. Bassini Hospital, 20092 Cinisello Balsamo, Italy. [email protected]
Norata Giuseppe Danilo
Catapano Alberico Luigi
References (97)
97 references, click to expand
  1. Oxidized low-density lipoprotein promotes mature dendritic cell transition from differentiating monocyte.
    J Immunol. 2001 Oct 1;167(7):3785-91 PMID: 11564795
  2. Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders.
    Cardiovasc Res. 2006 Jan;69(1):36-45 PMID: 16324688
  3. A candidate gene study revealed sex-specific association between the OLR1 gene and carotid plaque.
    Stroke. 2011 Mar;42(3):588-92 PMID: 21257822
  4. A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1.
    Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):360-4 PMID: 10618423
  5. Ox-LDL-induced LOX-1 expression in vascular smooth muscle cells: role of reactive oxygen species.
    Fundam Clin Pharmacol. 2011 Oct;25(5):572-9 PMID: 21077940
  6. Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles.
    Atherosclerosis. 2010 Jan;208(1):177-82 PMID: 19619878
  7. In vivo and in vitro studies support that a new splicing isoform of OLR1 gene is protective against acute myocardial infarction.
    Circ Res. 2005 Jul 22;97(2):152-8 PMID: 15976314
  8. Diabetes enhances lectin-like oxidized LDL receptor-1 (LOX-1) expression in the vascular endothelium: possible role of LOX-1 ligand and AGE.
    Biochem Biophys Res Commun. 2001 Oct 5;287(4):962-8 PMID: 11573959
  9. Redox-sensitive regulation of lox-1 gene expression in vascular endothelium.
    Biochem Biophys Res Commun. 2001 Mar 2;281(3):720-5 PMID: 11237717
  10. Oxidized LDL modulates Bax/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells.
    Arterioscler Thromb Vasc Biol. 2001 Jun;21(6):955-60 PMID: 11397703
  11. Oxidized low density lipoprotein potentiation of Fas-induced apoptosis through lectin-like oxidized-low density lipoprotein receptor-1 in human umbilical vascular endothelial cells.
    Circ J. 2002 Nov;66(11):1060-4 PMID: 12419941
  12. Cholesterol-lowering drugs inhibit lectin-like oxidized low-density lipoprotein-1 receptor function by membrane raft disruption.
    Mol Pharmacol. 2012 Aug;82(2):246-54 PMID: 22570368
  13. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transcriptional regulation by Oct-1 in human endothelial cells: implications for atherosclerosis.
    Biochem J. 2006 Jan 1;393(Pt 1):255-65 PMID: 16173915
  14. LOX-1 Inhibition in ApoE KO Mice Using a Schizophyllan-based Antisense Oligonucleotide Therapy.
    Mol Ther Nucleic Acids. 2012 Dec 04;1:e58 PMID: 23212297
  15. LOX-1 augments oxLDL uptake by lysoPC-stimulated murine macrophages but is not required for oxLDL clearance from plasma.
    J Lipid Res. 2009 Aug;50(8):1676-84 PMID: 19359704
  16. Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1.
    J Cell Sci. 2011 Dec 1;124(Pt 23):4115-24 PMID: 22135361
  17. Small concentrations of oxLDL induce capillary tube formation from endothelial cells via LOX-1-dependent redox-sensitive pathway.
    Arterioscler Thromb Vasc Biol. 2007 Nov;27(11):2435-42 PMID: 17717293
  18. LOX-1 and angiotensin receptors, and their interplay.
    Cardiovasc Drugs Ther. 2011 Oct;25(5):401-17 PMID: 21861069
  19. An oxidized low-density lipoprotein receptor gene variant is inversely associated with the severity of coronary artery disease.
    Clin Cardiol. 2004 Nov;27(11):641-4 PMID: 15562935
  20. Oxidized LDL through LOX-1 modulates LDL-receptor expression in human coronary artery endothelial cells.
    Biochem Biophys Res Commun. 2003 Aug 8;307(4):1008-12 PMID: 12878212
  21. 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. 1999 Feb 15;57(4):383-6 PMID: 9933026
  22. Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions.
    Circulation. 1999 Jun 22;99(24):3110-7 PMID: 10377073
  23. Effects of ox-LDL on number and activity of circulating endothelial progenitor cells.
    Drug Chem Toxicol. 2004 Aug;27(3):243-55 PMID: 15478946
  24. The 'PAI-1 paradox' in vascular remodeling.
    Thromb Haemost. 2008 Dec;100(6):984-91 PMID: 19132221
  25. Unique repetitive sequence and unexpected regulation of expression of rat endothelial receptor for oxidized low-density lipoprotein (LOX-1).
    Biochem J. 1998 Mar 15;330 ( Pt 3):1417-22 PMID: 9494115
  26. Ox-LDL plays dual effect in modulating expression of inflammatory molecules through LOX-1 pathway in human umbilical vein endothelial cells.
    Front Biosci. 2005 Sep 01;10:2585-94 PMID: 15970520
  27. Oxidized LDL: diversity, patterns of recognition, and pathophysiology.
    Antioxid Redox Signal. 2010 Jul 1;13(1):39-75 PMID: 19888833
  28. LOX-1 mediates oxidized low-density lipoprotein-induced expression of matrix metalloproteinases in human coronary artery endothelial cells.
    Circulation. 2003 Feb 4;107(4):612-7 PMID: 12566375
  29. Role of caspases in Ox-LDL-induced apoptotic cascade in human coronary artery endothelial cells.
    Circ Res. 2004 Feb 20;94(3):370-6 PMID: 14684629
  30. Oxidized low-density lipoprotein-dependent endothelial arginase II activation contributes to impaired nitric oxide signaling.
    Circ Res. 2006 Oct 27;99(9):951-60 PMID: 17008605
  31. Upregulation of endothelial receptor for oxidized LDL (LOX-1) by oxidized LDL and implications in apoptosis of human coronary artery endothelial cells: evidence from use of antisense LOX-1 mRNA and chemical inhibitors.
    Arterioscler Thromb Vasc Biol. 2000 Apr;20(4):1116-22 PMID: 10764682
  32. LOX-1/LOXIN: the yin/yang of atheroscleorosis.
    Cardiovasc Drugs Ther. 2011 Oct;25(5):489-94 PMID: 21904818
  33. LOX-1 in atherosclerosis: biological functions and pharmacological modifiers.
    Cell Mol Life Sci. 2013 Aug;70(16):2859-72 PMID: 23124189
  34. Expression of lectin-like oxidized low-density lipoprotein receptors during ischemia-reperfusion and its role in determination of apoptosis and left ventricular dysfunction.
    J Am Coll Cardiol. 2003 Mar 19;41(6):1048-55 PMID: 12651056
  35. Oxidized LDL-activated platelets induce vascular inflammation.
    Semin Thromb Hemost. 2010 Mar;36(2):146-56 PMID: 20414829
  36. LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia-reperfusion.
    Cardiovasc Res. 2007 Nov 1;76(2):292-302 PMID: 17707356
  37. Is LOX-1 K167N polymorphism protective for coronary artery disease?
    In Vivo. 2009 Nov-Dec;23(6):969-73 PMID: 20023241
  38. Inflammation in atherosclerosis.
    Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2045-51 PMID: 22895665
  39. LOX-1 receptor blockade abrogates oxLDL-induced oxidative DNA damage and prevents activation of the transcriptional repressor Oct-1 in human coronary arterial endothelium.
    J Biol Chem. 2008 Jul 11;283(28):19456-64 PMID: 18390905
  40. Prominent lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1) expression in atherosclerotic lesions is associated with tissue factor expression and apoptosis in hypercholesterolemic rabbits.
    Biol Pharm Bull. 2008 Aug;31(8):1475-82 PMID: 18670075
  41. The platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1 reduces the intracellular concentration of nitric oxide in endothelial cells.
    J Am Coll Cardiol. 2003 Feb 5;41(3):499-507 PMID: 12575983
  42. Angiotensin II increases the expression of lectin-like oxidized low-density lipoprotein receptor-1 in human vascular smooth muscle cells via a lipoxygenase-dependent pathway.
    Am J Hypertens. 2005 Mar;18(3):299-307 PMID: 15797645
  43. OxLDL-dependent activation of arginase II is dependent on the LOX-1 receptor and downstream RhoA signaling.
    Atherosclerosis. 2011 Feb;214(2):279-87 PMID: 21130456
  44. Oxidized low-density lipoprotein-induced apoptosis.
    Biochim Biophys Acta. 2002 Dec 30;1585(2-3):213-21 PMID: 12531556
  45. Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction.
    Clin Exp Pharmacol Physiol. 2004 Jul;31(7):407-13 PMID: 15236625
  46. New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus.
    Life Sci. 2012 Oct 15;91(13-14):507-16 PMID: 22483688
  47. Small dense LDL and VLDL predict common carotid artery IMT and elicit an inflammatory response in peripheral blood mononuclear and endothelial cells.
    Atherosclerosis. 2009 Oct;206(2):556-62 PMID: 19376517
  48. Oxidized low-density lipoprotein inhibits vascular endothelial growth factor-induced endothelial progenitor cell differentiation.
    Clin Exp Pharmacol Physiol. 2003 Sep;30(9):665-70 PMID: 12940886
  49. oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation.
    Atherosclerosis. 2009 Aug;205(2):442-50 PMID: 19203752
  50. Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor.
    Biochem J. 1998 Aug 15;334 ( Pt 1):9-13 PMID: 9693095
  51. Oxidized low density lipoprotein receptor-1 mediates oxidized low density lipoprotein-induced apoptosis in human umbilical vein endothelial cells: role of reactive oxygen species.
    Vascul Pharmacol. 2007 Jul;47(1):1-9 PMID: 17433786
  52. The lectin-like oxidized low-density-lipoprotein receptor: a pro-inflammatory factor in vascular disease.
    Biochem J. 2008 Jan 15;409(2):349-55 PMID: 18092947
  53. Targeting of lectinlike oxidized low-density lipoprotein receptor 1 (LOX-1) with 99mTc-labeled anti-LOX-1 antibody: potential agent for imaging of vulnerable plaque.
    J Nucl Med. 2008 Oct;49(10):1677-85 PMID: 18794262
  54. Statins modulate oxidized low-density lipoprotein-mediated adhesion molecule expression in human coronary artery endothelial cells: role of LOX-1.
    J Pharmacol Exp Ther. 2002 Aug;302(2):601-5 PMID: 12130721
  55. The multi-functionality of CD40L and its receptor CD40 in atherosclerosis.
    Thromb Haemost. 2009 Aug;102(2):206-14 PMID: 19652870
  56. Matrix metalloproteinases in cardiovascular disease.
    Can J Cardiol. 2006 Feb;22 Suppl B:25B-30B PMID: 16498509
  57. Association between OLR1 K167N SNP and intima media thickness of the common carotid artery in the general population.
    PLoS One. 2012;7(2):e31086 PMID: 22347434
  58. Oxidized low-density lipoprotein activates p66Shc via lectin-like oxidized low-density lipoprotein receptor-1, protein kinase C-beta, and c-Jun N-terminal kinase kinase in human endothelial cells.
    Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):2090-7 PMID: 21817106
  59. Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after vascular injury.
    Biochem Biophys Res Commun. 2006 Mar 10;341(2):591-8 PMID: 16434026
  60. The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular Disease.
    Cardiol Res Pract. 2012;2012:632408 PMID: 22454776
  61. Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells.
    Biochem Biophys Res Commun. 1998 Jul 30;248(3):511-4 PMID: 9703956
  62. Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice.
    Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):871-7 PMID: 17272755
  63. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation.
    Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4754-9 PMID: 12665618
  64. Activation-dependent surface expression of LOX-1 in human platelets.
    Biochem Biophys Res Commun. 2001 Mar 23;282(1):153-8 PMID: 11263985
  65. Oxidized low density lipoprotein displaces endothelial nitric-oxide synthase (eNOS) from plasmalemmal caveolae and impairs eNOS activation.
    J Biol Chem. 1999 Nov 5;274(45):32512-9 PMID: 10542298
  66. An endothelial receptor for oxidized low-density lipoprotein.
    Nature. 1997 Mar 6;386(6620):73-7 PMID: 9052782
  67. LOX-1-dependent transcriptional regulation in response to oxidized LDL treatment of human aortic endothelial cells.
    Am J Physiol Cell Physiol. 2009 Jun;296(6):C1329-37 PMID: 19279231
  68. Upregulation of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression in human endothelial cells by modified high density lipoproteins.
    Biochem Biophys Res Commun. 2012 Nov 16;428(2):230-3 PMID: 23073138
  69. Functional analysis and molecular dynamics simulation of LOX-1 K167N polymorphism reveal alteration of receptor activity.
    PLoS One. 2009;4(2):e4648 PMID: 19247493
  70. Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-kappaB through an increased production of intracellular reactive oxygen species.
    J Biol Chem. 2000 Apr 28;275(17):12633-8 PMID: 10777555
  71. Deletion of LOX-1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet.
    Circ Res. 2007 Jun 8;100(11):1634-42 PMID: 17478727
  72. Role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the development of hypertensive organ damage.
    Clin Exp Nephrol. 2004 Sep;8(3):178-82 PMID: 15480893
  73. Inflammation and atherosclerosis.
    Annu Rev Pathol. 2006;1:297-329 PMID: 18039117
  74. The renin-angiotensin system modulates inflammatory processes in atherosclerosis: evidence from basic research and clinical studies.
    Mediators Inflamm. 2009;2009:752406 PMID: 19390623
  75. Oxidized-LDL through LOX-1 increases the expression of angiotensin converting enzyme in human coronary artery endothelial cells.
    Cardiovasc Res. 2003 Jan;57(1):238-43 PMID: 12504834
  76. oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21.
    Mediators Inflamm. 2012;2012:320953 PMID: 22619482
  77. Upregulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) by 15-lipoxygenase-modified LDL in endothelial cells.
    Atherosclerosis. 2011 Feb;214(2):331-7 PMID: 21130457
  78. Nitric oxide synthases: regulation and function.
    Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d PMID: 21890489
  79. Overexpression of lectin-like oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice.
    Circ Res. 2005 Jul 22;97(2):176-84 PMID: 15961718
  80. Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein.
    Circulation. 1999 Aug 31;100(9):899-902 PMID: 10468518
  81. The binding of oxidized low density lipoprotein (ox-LDL) to ox-LDL receptor-1 reduces the intracellular concentration of nitric oxide in endothelial cells through an increased production of superoxide.
    J Biol Chem. 2001 Apr 27;276(17):13750-5 PMID: 11278710
  82. Transmembrane signaling pathway mediates oxidized low-density lipoprotein-induced expression of plasminogen activator inhibitor-1 in vascular endothelial cells.
    Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1243-54 PMID: 18796547
  83. The nuclear factor NF-kappaB pathway in inflammation.
    Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a001651 PMID: 20457564
  84. LOX-1 mediates lysophosphatidylcholine-induced oxidized LDL uptake in smooth muscle cells.
    FEBS Lett. 2000 Feb 11;467(2-3):217-20 PMID: 10675541
  85. Endothelial progenitor cells in atherosclerosis.
    Front Biosci (Landmark Ed). 2012 Jun 01;17:2327-49 PMID: 22652782
  86. The splice variant LOXIN inhibits LOX-1 receptor function through hetero-oligomerization.
    J Mol Cell Cardiol. 2008 Mar;44(3):561-70 PMID: 18191942
  87. LOX-1, an oxidized LDL endothelial receptor, induces CD40/CD40L signaling in human coronary artery endothelial cells.
    Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):816-21 PMID: 12637341
  88. Induction of endothelin-1 production in endothelial cells via co-operative action between CD40 and lectin-like oxidized LDL receptor (LOX-1).
    J Cardiovasc Pharmacol. 2004 Nov;44 Suppl 1:S173-80 PMID: 15838273
  89. LOX-1 abrogation reduces myocardial ischemia-reperfusion injury in mice.
    J Mol Cell Cardiol. 2008 Jan;44(1):76-83 PMID: 18022184
  90. The oral anti-diabetic agent, gliclazide, inhibits oxidized LDL-mediated LOX-1 expression, metalloproteinase-9 secretion and apoptosis in human aortic endothelial cells.
    Atherosclerosis. 2009 May;204(1):40-6 PMID: 18801483
  91. Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells.
    Circulation. 2000 Jun 27;101(25):2889-95 PMID: 10869259
  92. EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling.
    J Appl Physiol (1985). 2010 Jun;108(6):1745-56 PMID: 20203069
  93. Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy.
    Circulation. 2001 Oct 9;104(15):1767-72 PMID: 11591612
  94. Association of single nucleotide polymorphisms in the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction.
    J Med Genet. 2003 Dec;40(12):933-6 PMID: 14684693
  95. Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase.
    J Lipid Res. 2006 Jun;47(6):1227-37 PMID: 16522925
  96. Oxidized low density lipoprotein-induced transdifferentiation of bone marrow-derived smooth muscle-like cells into foam-like cells in vitro.
    Int J Exp Pathol. 2010 Feb;91(1):24-33 PMID: 20096071
  97. Oxidized LDL receptor gene (OLR1) is associated with the risk of myocardial infarction.
    Biochem Biophys Res Commun. 2003 Mar 28;303(1):247-50 PMID: 12646194
Article Info
Journal
Mediators of inflammation
Abbr.
Mediators Inflamm
ISSN
1466-1861
DOI
10.1155/2013/152786
Email
[email protected]
Published
2013-00-00
Epub
2013-00-10
Pages
152786
Language
English
Region
United States
NLM ID
9209001
PMCID
PMC3723318
Subset
IM
External Links
PubMed source DOI: 10.1155/2013/152786 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2