Affinage

OLR1

Oxidized low-density lipoprotein receptor 1 · UniProt P78380

Length
273 aa
Mass
31.0 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OLR1/LOX-1 is a Type II transmembrane C-type lectin-like scavenger receptor whose C-terminal lectin domain mediates recognition and internalization of multiple ligands, driving vascular inflammation and atherogenesis (PMID:12163130, PMID:24419805). Its lectin-like extracellular domain is N-glycosylated, and active-site mutagenesis identified conserved positively charged residues required for oxidized LDL binding; the domain also binds phosphatidylserine in a strictly Ca2+-dependent manner (enabling apoptotic-body recognition), adheres Gram-positive and Gram-negative bacteria independently of divalent cations, and serves as a receptor for H. pylori catalase to mediate gastric colonization (PMID:12163130, PMID:11290792, PMID:16146427, PMID:38253620). Ligand engagement activates p38-MAPK and NF-κB signaling and ROS generation, upregulating adhesion molecules (VCAM-1, ICAM-1) and impairing eNOS; endothelial-specific LOX-1 overexpression is sufficient to drive macrophage accumulation and atherosclerotic plaque formation in vivo (PMID:24419805, PMID:30819724). Downstream of receptor activation, LOX-1-generated ROS cause mitochondrial DNA damage and autophagy that activate the NLRP3 inflammasome, regulate calpain-1/calpain-2 balance and intracellular Ca2+ to control macrophage migration, and engage the NOX2/NOX4 axis in cardiomyocyte hypertrophy (PMID:24776598, PMID:26393906, PMID:28259654). LOX-1 is subject to multilayered control: ADAM10-mediated ectodomain shedding releases soluble LOX-1 and leaves a membrane N-terminal fragment that self-associates and activates MAP kinases ligand-independently until cleared by SPPL2a/b intramembrane proteolysis; HRD1-dependent ubiquitination targets it for proteasomal degradation; and the splice variant LOXIN hetero-oligomerizes with LOX-1 to reduce its surface expression (PMID:18191942, PMID:30819724, PMID:32308114). Its expression is transcriptionally driven by Oct-1, NF-κB, HIF-1α, and Nrf2 through defined promoter elements, repressed by SIRT1 via NF-κB suppression, and post-transcriptionally tuned by miR-98, miR-24, miR-590-5p, and m6A methylation (PMID:20418343, PMID:21796333, PMID:29549823, PMID:35299056). LOX-1 engages in mutual positive regulation with PCSK9 initiated by mitochondrial ROS, and statins directly bind its lectin-domain hydrophobic tunnel to displace ox-LDL and stabilize the receptor dimer (PMID:26092101, PMID:25950192). Beyond the vasculature, OLR1 promotes proliferation and metastasis of pancreatic and breast cancer cells through c-Myc/HMGA2 induction and NF-κB target gene activation (PMID:32019809, PMID:28844714, PMID:21637860).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2001 High

    Established that LOX-1 is a pattern-recognition receptor with ligand breadth beyond oxidized LDL, binding bacteria independently of cations or serum.

    Evidence FITC-labeled bacterial binding to LOX-1-expressing CHO-K1 and aortic endothelial cells with antibody/inhibitor blockade

    PMID:11290792

    Open questions at the time
    • Binding motif on bacteria not defined
    • physiological consequence of bacterial binding not addressed
  2. 2001 Medium

    Linked statins to LOX-1 by showing they suppress ox-LDL-induced LOX-1 upregulation and downstream MAP kinase activation, framing a cardioprotective mechanism.

    Evidence Western blotting for LOX-1/eNOS and MAP kinase assays in human coronary artery endothelial cells with two statins

    PMID:11735125

    Open questions at the time
    • No genetic confirmation
    • did not distinguish transcriptional vs post-translational effects
  3. 2002 High

    Defined the structural basis of ligand recognition, locating the functional binding determinants in the C-type lectin domain and documenting glycosylation and ectodomain shedding.

    Evidence Active-site mutagenesis, glycosylation studies, and cleavage/shedding assays

    PMID:12163130

    Open questions at the time
    • Sheddase identity not established here
    • no atomic structure of ligand-bound domain
  4. 2006 High

    Showed LOX-1 directly and selectively recognizes phosphatidylserine in a Ca2+-dependent manner, providing a molecular basis for apoptotic-cell clearance.

    Evidence Recombinant folded glycosylated protein lipid-specificity panel, Ca2+/Mg2+ substitution, apoptotic-body recognition with blocking antibodies

    PMID:16146427

    Open questions at the time
    • Ca2+ coordination site not mapped
    • in vivo relevance of PS recognition not tested
  5. 2007 High

    Identified a dominant-negative regulatory mechanism whereby the splice variant LOXIN suppresses LOX-1 by hetero-oligomerization and reduced surface localization.

    Evidence Reciprocal Co-IP and ox-LDL uptake/membrane localization assays in fibroblasts and endothelial cells

    PMID:18191942

    Open questions at the time
    • Stoichiometry of hetero-oligomers unknown
    • endogenous LOXIN regulation not defined
  6. 2010 High

    Placed SIRT1 as a negative regulator of LOX-1, reducing macrophage foam cell formation through NF-κB suppression.

    Evidence SIRT1 heterozygous and bone-marrow-restricted deletion in atherosclerotic mice with macrophage oxLDL uptake assays

    PMID:20418343

    Open questions at the time
    • Direct SIRT1 target at the OLR1 locus not defined
    • deacetylation substrate in the pathway unidentified
  7. 2011 Medium

    Mapped stimulus-specific transcriptional control of OLR1, identifying an Oct-1 element responding to ox-LDL and an NF-κB element responding to angiotensin II, defining a feed-forward loop.

    Evidence Promoter mapping, transcription-factor binding-site analysis, reporter assays

    PMID:21796333

    Open questions at the time
    • ChIP confirmation of Oct-1 occupancy not shown
    • in vivo relevance of specific sites not tested
  8. 2011 Medium

    Extended OLR1 function to oncogenesis, showing it activates NF-κB target genes promoting survival, cell cycle, and migration in breast epithelial/cancer cells.

    Evidence Overexpression, KO mouse transcriptome microarray, neutralizing antibody, adhesion/transendothelial migration assays

    PMID:21637860

    Open questions at the time
    • Ligand driving tumor NF-κB activation unclear
    • mechanism of surface signaling in cancer not dissected
  9. 2013 Medium

    Revealed a non-scavenging role in which LOX-1 supports cytoskeletal organization and proliferation in cardiac fibroblasts, declining with senescence.

    Evidence LOX-1 cDNA rescue of senescent fibroblasts with CDC42/p70S6K/Mdm2/Akt readouts and cytoskeleton imaging

    PMID:23648807

    Open questions at the time
    • No KO comparison
    • direct link from receptor to cytoskeletal effectors not established
  10. 2014 High

    Demonstrated that endothelial LOX-1 alone is sufficient to drive atherosclerosis via p38/NF-κB, ROS, VCAM-1, and eNOS impairment.

    Evidence Endothelial-specific Tie2 transgenic mice on ApoE-/- background with bone marrow transplantation epistasis and intravital imaging

    PMID:24419805

    Open questions at the time
    • Relative contribution of macrophage LOX-1 not isolated here
    • structural basis of receptor signaling not addressed
  11. 2014 Medium

    Defined an ordered intracellular cascade by which LOX-1-driven ROS cause mtDNA damage and autophagy to activate the NLRP3 inflammasome.

    Evidence siRNA, blocking antibody, ROS/autophagy modulators, and DNase II knockdown in THP-1 and primary macrophages

    PMID:24776598

    Open questions at the time
    • Single lab
    • in vivo confirmation of the inflammasome axis not shown
  12. 2014 Medium

    Showed LPS induces LOX-1 through a defined TLR4/MyD88/Nox4-ROS/p38/NF-κB hierarchy, connecting innate immune signaling to receptor upregulation.

    Evidence siRNA of TLR4/MyD88/Nox4, pathway inhibitors, ox-LDL uptake and monocyte adhesion assays, in vivo LPS injection

    PMID:25135647

    Open questions at the time
    • Direct promoter target downstream of NF-κB not mapped here
    • single lab
  13. 2014 Medium

    Implicated the LOX-1 pathway in myocardial ischemia-reperfusion injury, with induction specific to reperfusion and antibody blockade halving infarct size.

    Evidence Rat coronary ligation/reperfusion model with anti-LOX-1 mAb and infarct quantification

    PMID:12507499

    Open questions at the time
    • Ligand driving reperfusion induction unclear
    • single intervention method
  14. 2015 High

    Established reciprocal positive regulation between LOX-1 and PCSK9 initiated by mitochondrial ROS, linking two atherogenic factors.

    Evidence Bidirectional siRNA/overexpression/recombinant protein in cells confirmed in LOX-1 KO and PCSK9 KO mice with mtROS inhibitors

    PMID:26092101

    Open questions at the time
    • Molecular mediator of the cross-regulation not identified
    • whether interaction is direct or indirect unresolved
  15. 2015 Medium

    Showed statins directly bind the LOX-1 lectin-domain hydrophobic tunnel, displacing ox-LDL and stabilizing the receptor dimer.

    Evidence Cell-based ox-LDL displacement, molecular docking/dynamics, and electrophoresis/western blot of dimer assembly

    PMID:25950192

    Open questions at the time
    • No crystal structure
    • binding residues not validated by mutagenesis
  16. 2015 Medium

    Identified cholesterol-dependent release routes for LOX-1, including exosomal export of full-length receptor and metalloproteinase-mediated ectodomain shedding enhanced by statins.

    Evidence MβCD/statin cholesterol modulation, exosome isolation, metalloproteinase inhibition, western blotting in endothelial cells

    PMID:26495844

    Open questions at the time
    • Specific metalloproteinase not identified here
    • functional role of exosomal LOX-1 unclear
  17. 2015 Medium

    Connected a 3'UTR SNP (rs1050286) to allele-specific miR-24 repression of OLR1, providing a genetic mechanism for expression variation.

    Evidence Luciferase assays with OLR1 3'UTR alleles and miR-24 overexpression in genotyped cell lines

    PMID:26542080

    Open questions at the time
    • Population-level phenotype not linked
    • single lab
  18. 2015 Medium

    Showed LOX-1 controls macrophage migration via calpain-1/calpain-2 balance and intracellular Ca2+ in response to ox-LDL.

    Evidence LOX-1 KO peritoneal macrophages, calpain western blotting, migration and Ca2+ assays

    PMID:26393906

    Open questions at the time
    • Mechanism linking receptor to calpain switch not defined
    • single lab
  19. 2016 Medium

    Identified miR-590-5p as a repressor of LOX-1 protecting endothelial cells from angiotensin II-induced apoptosis and ROS.

    Evidence miR-590-5p mimics, LOX-1 siRNA/neutralizing antibody, apoptosis flow cytometry, caspase-3/cytochrome C western blotting

    PMID:26906623

    Open questions at the time
    • Direct 3'UTR binding validation limited
    • in vivo confirmation absent
  20. 2016 Medium

    Extended hypoxia-driven LOX-1 signaling to microglia, with ChIP-confirmed NF-κB and HIF-1α promoter binding and an autonomous positive-feedback loop.

    Evidence Oxygen-glucose deprivation in primary microglia, ChIP, luciferase reporters, siRNA and pathway inhibitors

    PMID:37268943

    Open questions at the time
    • In vivo neuroinflammation relevance not tested
    • single cell type
  21. 2016 Medium

    Implicated LOX-1 in hypoxia-induced cardiomyocyte hypertrophy through a NOX2/NOX4/ROS pathway.

    Evidence LOX-1 siRNA in H9C2 cells and rat hypoxia model with hypertrophy and ROS readouts

    PMID:28259654

    Open questions at the time
    • Receptor ligand in hypoxia unclear
    • single lab
  22. 2017 Medium

    Showed OLR1 promotes pancreatic cancer proliferation and metastasis through a c-Myc/HMGA2 transcriptional axis.

    Evidence Overexpression/knockdown in pancreatic cancer lines, xenograft model, c-Myc/HMGA2 expression analysis

    PMID:32019809

    Open questions at the time
    • Link from surface receptor to c-Myc induction not mechanistically resolved
    • single lab
  23. 2017 Medium

    Placed OLR1 downstream of the TBC1D3 oncogene via TNFα/NF-κB signaling driving breast cancer migration.

    Evidence TBC1D3 overexpression, OLR1 siRNA/pomalidomide, NF-κB inhibitor, migration assays

    PMID:28844714

    Open questions at the time
    • Direct OLR1 promoter occupancy not shown
    • single lab
  24. 2019 High

    Resolved the proteolytic fate of LOX-1, showing ADAM10 sheds the ectodomain and SPPL2a/b clear the residual NTF, which otherwise self-associates to activate MAP kinases ligand-independently and drive atherosclerosis.

    Evidence SPPL2a/b knockout mice, biochemical characterization of NTF, MAP kinase assays, plaque quantification

    PMID:30819724

    Open questions at the time
    • Structural basis of NTF self-association undefined
    • regulation of ADAM10 shedding in vivo not detailed
  25. 2020 Medium

    Identified HRD1 as the E3 ligase ubiquitinating LOX-1 for proteasomal degradation, with KLF2-driven HRD1 protecting endothelium from ox-LDL-induced apoptosis.

    Evidence Co-IP, ubiquitination assay, HRD1 overexpression/LOX-1 siRNA, apoptosis assay, KLF2 promoter binding

    PMID:32308114

    Open questions at the time
    • Ubiquitination site on LOX-1 not mapped
    • single lab
  26. 2022 Medium

    Established Nrf2 as a direct positive transcriptional regulator of LOX-1 promoting VSMC proliferation and plaque burden.

    Evidence Dual luciferase reporter, immunoprecipitation, Nrf2 siRNA in VSMCs, ApoE-/-Nrf2-/- double-knockout mice

    PMID:35299056

    Open questions at the time
    • Exact Nrf2 response element not delineated
    • single lab
  27. 2023 Medium

    Connected Klotho-dependent IGF-1R/RAC1 signaling to OLR1 suppression, reducing ox-LDL deposition in diabetic kidney podocytes.

    Evidence Klotho genotype STZ-DKD mouse model and podocyte IGF-1R/RAC1 siRNA/inhibitor experiments

    PMID:37891556

    Open questions at the time
    • Direct transcriptional control of OLR1 not shown
    • single lab
  28. 2024 High

    Identified LOX-1 as the host receptor for H. pylori catalase mediating gastric colonization, and showed METTL3-driven m6A destabilizes OLR1 mRNA.

    Evidence m6A-seq, METTL3 siRNA/Mettl3 hemizygous mice, LOX-1 inhibition/knockout, bacterial catalase deletion adhesion assays

    PMID:38253620

    Open questions at the time
    • Catalase-binding interface on LOX-1 not mapped
    • downstream signaling from this interaction not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LOX-1's diverse ligand recognition is structurally encoded and translated into distinct downstream signaling outputs across cell types remains unresolved.
  • No high-resolution structure of ligand-bound LOX-1
  • no defined transmembrane signaling adaptor for the receptor
  • mechanism distinguishing ligand-dependent from NTF-mediated signaling unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 4 GO:0001618 virus receptor activity 2 GO:0060089 molecular transducer activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-392499 Metabolism of proteins 2
Partners
ADAM10HRD1LOXINPCSK9SPPL2ASPPL2B

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 LOX-1 is a Type II transmembrane protein with a C-type lectin-like extracellular domain; mutagenesis studies revealed that the lectin domain is the functional domain recognizing LOX-1 ligands, with C-terminal end residues and conserved positively charged residues spanning the lectin domain essential for OxLDL binding. The extracellular domains are post-translationally modified by N-linked glycosylation. LOX-1 can be cleaved by a protease at the extracellular juxtamembrane region to release a soluble form (sLOX-1). Active-site mutagenesis, glycosylation studies, cleavage/shedding assays Pharmacology & therapeutics High 12163130
2001 LOX-1 supports adhesion of both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria to CHO-K1 cells stably expressing LOX-1 and to bovine aortic endothelial cells; binding was suppressed by poly(I) and anti-LOX-1 mAb, does not require divalent cations or serum factors, and functions under static and nonstatic conditions. Stable expression in CHO-K1 cells, FITC-labeled bacterial binding assay, antibody/inhibitor blockade Journal of immunology High 11290792
2006 LOX-1 recognizes phosphatidylserine (PS) in a Ca2+-dependent manner; a recombinant, folded, and glycosylated LOX-1 binds PS but not other phospholipids; Ca2+ is specifically required (Mg2+ cannot substitute); LOX-1-mediated recognition of PS-containing apoptotic bodies was Ca2+-dependent and was abolished by bivalent-cation chelation, LOX-1-blocking antibodies, or PS-containing liposomes. Recombinant protein binding assay, lipid binding specificity panel, Ca2+/Mg2+ substitution experiments, apoptotic body recognition assay with antibody blockade The Biochemical journal High 16146427
2007 The naturally occurring splice variant LOXIN (lacking part of the C-terminus lectin-like domain) inhibits LOX-1 function through hetero-oligomerization: LOXIN co-immunoprecipitates with LOX-1, forming non-functional hetero-oligomers that decrease LOX-1 plasma membrane localization and markedly impair ox-LDL binding and uptake. Co-immunoprecipitation, co-transfection of LOX-1 and LOXIN in mammalian fibroblasts and human endothelial cells, fluorescent ox-LDL uptake assay, plasma membrane localization assessment Journal of molecular and cellular cardiology High 18191942
2014 Endothelial-specific LOX-1 overexpression (using Tie2 promoter transgenic mice) increased aortic oxLDL uptake in endothelial cells but not macrophages, led to p38 phosphorylation, increased NF-κB activity and VCAM-1 upregulation, increased ROS production, impaired eNOS activity, and promoted macrophage accumulation and atherosclerotic plaque formation. Bone marrow transplantation showed endothelial LOX-1 alone was sufficient for atherosclerosis development. Endothelial-specific transgenic mouse model (Tie2 promoter), ApoE-/- double-mutant, bone marrow transplantation, western blotting, intravital imaging European heart journal High 24419805
2010 SIRT1 reduces macrophage foam cell formation by diminishing LOX-1 expression via suppression of the NF-κB signaling pathway; partial SIRT1 deletion in atherosclerotic mice increased oxLDL accumulation in peritoneal macrophages and promoted foam cell formation; bone marrow-restricted SIRT1 deletion confirmed macrophage-specific SIRT1 function decreases atherogenesis through LOX-1. Heterozygous SIRT1 mouse model, bone marrow transplantation, peritoneal macrophage isolation, oxLDL uptake assays, NF-κB pathway analysis European heart journal High 20418343
2015 All tested statins directly interact with the LOX-1 C-type lectin-like domain (CTLD), filling a hydrophobic tunnel in the recognition domain, displacing fluorescent ox-LDL binding. This interaction stabilizes the LOX-1 dimer, as confirmed by electrophoresis and western blot. Molecular docking and molecular dynamics simulations identified a 'CTLD clamp motion' enabling receptor-substrate coupling. Cell-based fluorescent ox-LDL displacement assay, molecular docking simulation, molecular dynamics simulation, electrophoretic separation and western blot of dimer assembly Cell cycle Medium 25950192
2019 SPPL2a/b (signal peptide peptidase-like 2a/b) perform intramembrane proteolysis of the membrane-bound N-terminal fragment (NTF) of LOX-1 generated after ectodomain shedding by ADAM10 and lysosomal degradation. LOX-1 NTFs self-associate via their transmembrane domain and activate MAP kinases in a ligand-independent manner, upregulating pro-atherogenic targets (ICAM-1, CTGF). SPPL2a/b-deficient mice accumulate LOX-1 NTFs and develop larger atherosclerotic plaques. Genetic mouse models (SPPL2a/b knockout), biochemical characterization of LOX-1 NTF, MAP kinase activation assays, identification of ADAM10 as sheddase, immunofluorescence, atherosclerosis plaque quantification The Journal of experimental medicine High 30819724
2014 LOX-1-mediated ROS generation drives autophagy and mitochondrial DNA (mtDNA) damage, which in turn activates the NLRP3 inflammasome in THP-1 macrophages and primary macrophages; LOX-1 inhibition (by blocking antibody or siRNA) inhibited ROS generation, autophagy, mtDNA damage, and NLRP3 inflammasome expression. DNase II knockdown also inhibited autophagy and NLRP3, confirming the pathway: LOX-1 → ROS → mtDNA damage → autophagy → NLRP3 activation. siRNA knockdown, blocking antibody, ROS inhibitors, autophagy inducer/inhibitor, DNase II siRNA, THP-1 and primary macrophages Cardiovascular research Medium 24776598
2015 LOX-1 and PCSK9 positively regulate each other's expression; siRNA knockdown of PCSK9 reduced LOX-1 expression and function, while recombinant PCSK9 enhanced LOX-1 expression; conversely, LOX-1 siRNA reduced PCSK9 expression and LOX-1 overexpression increased PCSK9. In LOX-1 KO mice, PCSK9 was decreased; in PCSK9 KO mice, LOX-1 was decreased. Mitochondrial ROS (mtROS) initiates the LOX-1/PCSK9 interaction. siRNA knockdown, cDNA overexpression, recombinant protein treatment, LOX-1 KO and PCSK9 KO mouse models, western blotting, mtROS inhibitors Cardiovascular research High 26092101
2014 LOX-1 pathway activation is involved in determining the extent of myocardial ischemia-reperfusion injury; LOX-1 expression is induced in cardiac myocytes following ischemia-reperfusion (but not ischemia alone). Administration of anti-LOX-1 monoclonal antibody reduced myocardial infarction size by ~50% in rats. Rat coronary artery ligation/reperfusion model, immunohistochemistry, anti-LOX-1 monoclonal antibody treatment, infarct size measurement Biochemical and biophysical research communications Medium 12507499
2001 Statins (simvastatin and atorvastatin) attenuate ox-LDL-induced upregulation of LOX-1 and downregulation of eNOS in human coronary artery endothelial cells; ox-LDL-mediated MAP kinase activation was also inhibited by statins, suggesting inhibition of LOX-1 and subsequently MAP kinase activity as a mechanism of statin cardioprotection. Cell-based assay with human coronary artery endothelial cells, western blotting for LOX-1 and eNOS, MAP kinase activation assay, dose-response with two different statins Biochemical and biophysical research communications Medium 11735125
2014 LPS induces LOX-1 expression via the TLR4/MyD88/Nox4-ROS/p38MAPK/NF-κB signaling pathway in endothelial cells; siRNA for TLR4, MyD88, and Nox4 each blocked LPS-induced LOX-1 upregulation, as did inhibitors of p38MAPK, NF-κB, and NADPH oxidase. LOX-1-mediated ox-LDL uptake and monocyte-endothelial adhesion were inhibited by anti-LOX-1 antibody. siRNA knockdown of TLR4, MyD88, Nox4; pharmacological inhibitors; western blotting; DiI-ox-LDL uptake assay; monocyte adhesion assay; in vivo mouse LPS injection Vascular pharmacology Medium 25135647
2015 LOX-1 inhibition impairs macrophage migration in response to ox-LDL; LOX-1 mediates ox-LDL-induced upregulation of calpain-2 and downregulation of calpain-1, and increases intracellular Ca2+; LOX-1 knockout macrophages show higher calpain-1 expression, lower calpain-2, improved migration, and lower Ca2+ compared to wild-type after ox-LDL treatment. LOX-1 knockout mouse peritoneal macrophages, wild-type comparison, calpain expression western blotting, cell migration assay, intracellular Ca2+ measurement Biochemical and biophysical research communications Medium 26393906
2015 Membrane cholesterol depletion (by MβCD) triggers release of full-length LOX-1 in exosomes and promotes ectodomain shedding to generate soluble LOX-1 (sLOX-1); endothelial cells secrete a soluble metalloproteinase responsible for LOX-1 ectodomain shedding; long-term statin treatment enhances sLOX-1 proteolytic shedding. Cholesterol modulation by MβCD and statins, exosome isolation, western blotting for full-length and truncated forms, metalloproteinase inhibition assay, stable and transient LOX-1 expression in endothelial cells PloS one Medium 26495844
2011 LOX-1 transcription is upregulated by ox-LDL through an Oct-1 binding motif at nt -1556 of the human LOX-1 promoter, and by angiotensin II through an NF-κB motif at nt -2158; Oct-1-mediated upregulation represents an early transcriptional event in LOX-1 stimulation by ox-LDL, creating a positive feedback loop. Promoter analysis, transcription factor binding site mapping, reporter assays Cardiovascular drugs and therapy Medium 21796333
2018 miR-98 directly targets LOX-1 mRNA (validated by luciferase reporter assay); miR-98 mimics decreased LOX-1 expression and inhibited foam cell formation and lipid accumulation in macrophages; miR-98 inhibitors had opposite effects; effects confirmed in ApoE-/- mice in vivo. Luciferase reporter assay (3'UTR), miR-98 mimics and inhibitors in peritoneal macrophages, ApoE-/- mouse model with agomiR-98 and antagomiR-98 Redox biology High 29549823
2015 The rs1050286 SNP in the OLR1 3'UTR alters LOX-1 expression by modifying miR-24 binding affinity; luciferase assays showed miR-24 targets OLR1 3'UTR-G but not 3'UTR-A; overexpression of miR-24 in HeLa cells (heterozygous A/G) but not HepG2 cells (homozygous A/A) significantly downregulated OLR1 mRNA and protein. Luciferase reporter assay with OLR1 3'UTR alleles, miR-24 overexpression in genotyped cell lines, RT-PCR and western blotting Journal of cellular and molecular medicine Medium 26542080
2020 HRD1 (E3 ubiquitin ligase) interacts with LOX-1 and promotes ubiquitination and proteasomal degradation of LOX-1, thereby preventing ox-LDL-induced endothelial cell apoptosis; LOX-1 deletion attenuated endothelial apoptosis induced by HRD1 downregulation; transcription factor KLF2 positively regulates HRD1 expression and pravastatin enhanced HRD1 expression through a KLF2-dependent mechanism. Co-immunoprecipitation of HRD1 with LOX-1, ubiquitination assay, HRD1 overexpression and LOX-1 siRNA knockdown, endothelial apoptosis assay, KLF2/promoter binding assay Cell cycle Medium 32308114
2016 LOX-1 mediates inflammatory activation of microglial cells through the p38-MAPK/NF-κB pathway under hypoxic-ischemic conditions; NF-κB and HIF-1α bind to the OLR1 gene promoter region (confirmed by chromatin immunoprecipitation and luciferase reporter assay); LOX-1 expression in microglial cells is autonomously maintained by positive feedback of the intracellular LOX-1 signaling pathway. Primary rat microglial cells, oxygen-glucose deprivation model, siRNA, p38-MAPK inhibitor, NF-κB inhibitor, luciferase reporter assay, chromatin immunoprecipitation assay (ChIP), ROS assay, cytokine measurement Cell communication and signaling Medium 37268943
2022 Nrf2 directly binds to the LOX-1 promoter sequence and positively regulates LOX-1 transcriptional and translational activity; Nrf2 deficiency in ApoE-/- mice diminished LOX-1 expression and attenuated VSMC proliferation and migration, reducing atherosclerotic plaque burden; confirmed by dual luciferase reporter and immunoprecipitation assays. Dual luciferase reporter assay, immunoprecipitation, Nrf2-siRNA in VSMCs, Apoe-/-Nrf2-/- double knockout mouse model, proliferation and migration assays Atherosclerosis Medium 35299056
2024 LOX-1 acts as a membrane receptor for H. pylori catalase, mediating bacterial adhesion to gastric epithelial cells; LOX-1 mRNA is a key target regulated by m6A modification (added by METTL3), which destabilizes LOX-1 mRNA and reduces LOX-1 protein levels; pharmacological inhibition or genetic ablation of LOX-1 reduces H. pylori colonization; deletion of bacterial catalase decreases adhesion to human gastric sections. m6A-seq, siRNA against m6A methylases, Mettl3 hemizygous mouse model, LOX-1 pharmacological inhibition and genetic knockout, bacterial adhesion assay, identification of LOX-1 as receptor for H. pylori catalase Nature communications High 38253620
2016 LOX-1 knockdown in H9C2 cardiomyocytes significantly ameliorated hypoxia-induced cell hypertrophy and reduced oxidative stress; mechanistically, LOX-1/NOX2/NOX4/ROS pathway underlies hypoxia-induced right ventricular hypertrophy; LOX-1 knockdown attenuated NOX2/4 expression and ROS generation. siRNA knockdown of LOX-1 in H9C2 cells and rat model, immunofluorescence, western blotting, DCFH-DA ROS assay, rat hypoxia model Life sciences Medium 28259654
2017 OLR1 increases HMGA2 transcription by upregulating c-Myc expression to promote metastasis of pancreatic cancer cells; OLR1 promoted proliferation and metastasis in vitro and in vivo. OLR1 overexpression and knockdown in pancreatic cancer cell lines, in vivo xenograft mouse model, c-Myc and HMGA2 expression analysis Molecular cancer research Medium 32019809
2017 TBC1D3 oncogene upregulates OLR1 expression at the transcriptional level via activation of the TNFα/NF-κB signaling pathway; OLR1 depletion (by siRNA or pomalidomide) significantly decreased TBC1D3-induced migration of breast cancer cells; TBC1D3 increased TNFα release, elevated TNFR1/TRAF transcription, and decreased TNFR1 degradation to activate NF-κB. siRNA knockdown of OLR1, TBC1D3 overexpression, NF-κB inhibitor caffeic acid phenethyl ester, pomalidomide (TNFα inhibitor), cell migration assay Cancer letters Medium 28844714
2011 OLR1 overexpression activates NF-κB (p65) and upregulates pro-oncogenic NF-κB target genes involved in apoptosis inhibition (BCL2, BCL2A1, TNFAIP3) and cell cycle regulation (CCND2) in both MCF10A and HCC1143 cell lines; OLR1 overexpression in HCC1143 cells enhanced cell migration; OLR1 neutralizing antibody inhibited adhesion and transendothelial migration of untreated HCC1143 cells; OLR1 KO mice showed broad inhibition of NF-κB target genes and de novo lipogenesis genes. OLR1 overexpression, OLR1 KO mouse microarray, neutralizing antibody, cell migration assay, cell adhesion and transendothelial migration assay, transcriptome analysis PloS one Medium 21637860
2013 LOX-1 in cardiac fibroblasts supports cytoskeletal organization and proliferation; as fibroblasts senesce, LOX-1 expression decreases; transfection of senescent fibroblasts with h-LOX-1 restored cytoskeletal organization, partially restored CDC42 and p70 S6 kinase expression, enhanced proliferation, and restored Mdm2 and phospho-Akt expression. Serial passage and aging mouse cardiac fibroblast isolation, LOX-1 cDNA transfection, cytoskeleton imaging, western blotting for CDC42, p70 S6 kinase, Mdm2, Akt Journal of molecular and cellular cardiology Medium 23648807
2016 miR-590-5p targets LOX-1 mRNA; Ang II downregulates miR-590-5p and upregulates LOX-1 in HUVECs; miR-590-5p mimics reduced LOX-1 expression and attenuated Ang II-induced apoptosis and ROS generation; LOX-1 siRNA or neutralizing antibody (TS92) reduced apoptosis and inhibited caspase-3 activation and cytochrome C release. miR-590-5p mimics, LOX-1 siRNA, LOX-1 neutralizing antibody (TS92), flow cytometry for apoptosis, western blotting for caspase-3 and cytochrome C, DCFH-DA for ROS Biochemical and biophysical research communications Medium 26906623
2023 Klotho inhibits ox-LDL deposition in podocytes in diabetic kidney disease by reducing IGF-1R expression, which decreases RAC1 expression and enhances mitochondrial function, ultimately reducing OLR1 expression and renal ox-LDL deposition. Klotho genotype mouse model (STZ-induced DKD), in vitro podocyte experiments, siRNA/inhibitor targeting IGF-1R and RAC1, western blotting and immunofluorescence Cardiovascular diabetology Medium 37891556

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 LOX-1, OxLDL, and atherosclerosis. Mediators of inflammation 603 23935243
2002 LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis. Pharmacology & therapeutics 319 12163130
2019 Role of Ox-LDL and LOX-1 in Atherogenesis. Current medicinal chemistry 252 29737246
2011 Oxidized LDL, LOX-1 and atherosclerosis. Cardiovascular drugs and therapy 243 21947818
2012 LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cellular and molecular life sciences : CMLS 242 23124189
2019 LOX-1: Regulation, Signaling and Its Role in Atherosclerosis. Antioxidants (Basel, Switzerland) 205 31336709
2015 Cross-talk between LOX-1 and PCSK9 in vascular tissues. Cardiovascular research 205 26092101
2010 SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis. European heart journal 190 20418343
2020 PCSK9 and inflammation: role of shear stress, pro-inflammatory cytokines, and LOX-1. Cardiovascular research 184 31746997
2001 LOX-1 supports adhesion of Gram-positive and Gram-negative bacteria. Journal of immunology (Baltimore, Md. : 1950) 144 11290792
2017 LOX-1 in Atherosclerosis and Myocardial Ischemia: Biology, Genetics, and Modulation. Journal of the American College of Cardiology 143 28571642
2011 Oxidative stress and lectin-like ox-LDL-receptor LOX-1 in atherogenesis and tumorigenesis. Antioxidants & redox signaling 143 21338316
2011 The discovery of LOX-1, its ligands and clinical significance. Cardiovascular drugs and therapy 130 21805404
2014 LOX-1, mtDNA damage, and NLRP3 inflammasome activation in macrophages: implications in atherogenesis. Cardiovascular research 117 24776598
2018 LOX-1 receptor: A potential link in atherosclerosis and cancer. Life sciences 112 29462603
2015 Interplay between CRP, Atherogenic LDL, and LOX-1 and Its Potential Role in the Pathogenesis of Atherosclerosis. Clinical chemistry 102 26607724
2009 Lox-1: the multifunctional receptor underlying cardiovascular dysfunction. Circulation journal : official journal of the Japanese Circulation Society 101 19801851
2011 Oxidized LDL receptor 1 (OLR1) as a possible link between obesity, dyslipidemia and cancer. PloS one 100 21637860
2014 Endothelial overexpression of LOX-1 increases plaque formation and promotes atherosclerosis in vivo. European heart journal 95 24419805
2001 Inhibition of LOX-1 by statins may relate to upregulation of eNOS. Biochemical and biophysical research communications 95 11735125
2003 Oxidized LDL receptor gene (OLR1) is associated with the risk of myocardial infarction. Biochemical and biophysical research communications 92 12646194
2021 LOX-1 and cancer: an indissoluble liaison. Cancer gene therapy 89 33402733
2013 Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress. PloS one 89 23799016
2004 Proinflammatory cytokines regulate LOX-1 expression in vascular smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology 87 15271788
2019 Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer. Journal of hematology & oncology 85 31514732
2014 LOX-1 and ROS, inseparable factors in the process of endothelial damage. Free radical research 82 24886290
2006 LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells. The Biochemical journal 79 16146427
2018 Targeting LOX-1 in atherosclerosis and vasculopathy: current knowledge and future perspectives. Annals of the New York Academy of Sciences 77 30381837
2000 Expression of LOX-1, an oxidized low-density lipoprotein receptor, in experimental hypertensive glomerulosclerosis. Journal of the American Society of Nephrology : JASN 71 11004213
2019 LOX-1+ PMN-MDSC enhances immune suppression which promotes glioblastoma multiforme progression. Cancer management and research 67 31447588
2007 The splice variant LOXIN inhibits LOX-1 receptor function through hetero-oligomerization. Journal of molecular and cellular cardiology 62 18191942
2011 LOX-1, oxidative stress and inflammation: a novel mechanism for diabetic cardiovascular complications. Cardiovascular drugs and therapy 61 21993919
2014 Lipopolysaccharide induced LOX-1 expression via TLR4/MyD88/ROS activated p38MAPK-NF-κB pathway. Vascular pharmacology 60 25135647
2016 LOX-1-Mediated Effects on Vascular Cells in Atherosclerosis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 59 27160316
2017 Up-regulation of OLR1 expression by TBC1D3 through activation of TNFα/NF-κB pathway promotes the migration of human breast cancer cells. Cancer letters 50 28844714
2020 OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2. Molecular cancer research : MCR 49 32019809
2016 Roles of LOX-1 in microvascular dysfunction. Microvascular research 47 26907636
2012 LOX-1: a multiligand receptor at the crossroads of response to danger signals. Current opinion in lipidology 47 22777292
2000 Oxidized-LDL and atherosclerosis. Role of LOX-1. Annals of the New York Academy of Sciences 47 10865829
2019 LOX-1 and atherosclerotic-related diseases. Clinica chimica acta; international journal of clinical chemistry 46 30639239
2014 LOX-1, oxidant stress, mtDNA damage, autophagy, and immune response in atherosclerosis. Canadian journal of physiology and pharmacology 46 24959993
2016 LOX-1 and TLR4 affect each other and regulate the generation of ROS in A. fumigatus keratitis. International immunopharmacology 43 27694040
2015 Molecular mechanism of statin-mediated LOX-1 inhibition. Cell cycle (Georgetown, Tex.) 43 25950192
2020 Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX-1 in apoE-/- mice. Experimental and therapeutic medicine 42 33262811
2019 Galectin-3 aggravates ox-LDL-induced endothelial dysfunction through LOX-1 mediated signaling pathway. Environmental toxicology 42 30963716
2011 LOX-1 and angiotensin receptors, and their interplay. Cardiovascular drugs and therapy 41 21861069
2003 LOX-1 pathway affects the extent of myocardial ischemia-reperfusion injury. Biochemical and biophysical research communications 41 12507499
2018 MicroRNA-98 regulates foam cell formation and lipid accumulation through repression of LOX-1. Redox biology 40 29549823
2017 Xanthine Oxidase Induces Foam Cell Formation through LOX-1 and NLRP3 Activation. Cardiovascular drugs and therapy 40 28084571
2015 Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein. Scientific reports 40 26578342
2014 LOX-1 in atherosclerotic disease. Clinica chimica acta; international journal of clinical chemistry 40 25463747
2017 LOX-1 and Its Splice Variants: A New Challenge for Atherosclerosis and Cancer-Targeted Therapies. International journal of molecular sciences 35 28146073
2019 Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis. The Journal of experimental medicine 34 30819724
2019 Upregulated LOX-1 Receptor: Key Player of the Pathogenesis of Atherosclerosis. Current atherosclerosis reports 34 31350594
2015 The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis. Scientific reports 34 26666837
2022 The oxidized-LDL/LOX-1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells. International journal of cancer 32 35608341
2013 Oxidized LDL and LOX-1 in experimental sepsis. Mediators of inflammation 32 24000272
2023 LOX-1 mediates inflammatory activation of microglial cells through the p38-MAPK/NF-κB pathways under hypoxic-ischemic conditions. Cell communication and signaling : CCS 31 37268943
2018 Wnt5a contributes to dectin-1 and LOX-1 induced host inflammatory response signature in Aspergillus fumigatus keratitis. Cellular signalling 31 30172652
2016 MiR-590-5p-meidated LOX-1 upregulation promotes Angiotensin II-induced endothelial cell apoptosis. Biochemical and biophysical research communications 31 26906623
2011 LOX-1 transcription. Cardiovascular drugs and therapy 31 21796333
2019 Targeting LOX-1 Inhibits Colorectal Cancer Metastasis in an Animal Model. Frontiers in oncology 30 31608230
2011 LOX-1 and obesity. Cardiovascular drugs and therapy 30 21881850
2004 The role of LOX-1, a novel lectin-like receptor for oxidized low density lipoprotein, in atherosclerosis. The Canadian journal of cardiology 29 15309203
2019 Wnt5a is involved in LOX-1 and TLR4 induced host inflammatory response in peri-implantitis. Journal of periodontal research 28 31593304
2020 HRD1 prevents atherosclerosis-mediated endothelial cell apoptosis by promoting LOX-1 degradation. Cell cycle (Georgetown, Tex.) 27 32308114
2019 Pro-oncogenic action of LOX-1 and its splice variant LOX-1Δ4 in breast cancer phenotypes. Cell death & disease 27 30718451
2006 Association of the OLR1 gene with milk composition in Holstein dairy cattle. Journal of dairy science 27 16606746
2023 Klotho inhibits renal ox-LDL deposition via IGF-1R/RAC1/OLR1 signaling to ameliorate podocyte injury in diabetic kidney disease. Cardiovascular diabetology 26 37891556
2011 Novel concepts in the genesis of hypertension: role of LOX-1. Cardiovascular drugs and therapy 26 21912849
2022 Myeloperoxidase-Oxidized LDL Activates Human Aortic Endothelial Cells through the LOX-1 Scavenger Receptor. International journal of molecular sciences 25 35269979
2022 Nrf2 deficiency attenuates atherosclerosis by reducing LOX-1-mediated proliferation and migration of vascular smooth muscle cells. Atherosclerosis 25 35299056
2011 Role of OLR1 and its regulating hsa-miR369-3p in Alzheimer's disease: genetics and expression analysis. Journal of Alzheimer's disease : JAD 25 21709374
2022 Reducing the Damage of Ox-LDL/LOX-1 Pathway to Vascular Endothelial Barrier Can Inhibit Atherosclerosis. Oxidative medicine and cellular longevity 24 35391927
2018 Toll-like receptor 2 activation primes and upregulates osteoclastogenesis via lox-1. Lipids in health and disease 24 29859535
2015 Membrane Cholesterol Modulates LOX-1 Shedding in Endothelial Cells. PloS one 24 26495844
2011 Angiogenesis is a link between atherosclerosis and tumorigenesis: role of LOX-1. Cardiovascular drugs and therapy 24 21968594
2013 Design of a novel LOX-1 receptor antagonist mimicking the natural substrate. Biochemical and biophysical research communications 23 23892036
2006 G501C polymorphism of oxidized LDL receptor gene (OLR1) and ischemic stroke. Brain research 23 17022953
2021 Effects of Apigenin on the Expression of LOX-1, Bcl-2, and Bax in Hyperlipidemia Rats. Chemistry & biodiversity 22 34118114
2020 LOX-1: A potential driver of cardiovascular risk in SLE patients. PloS one 22 32182251
2014 15-LOX-1 suppression of hypoxia-induced metastatic phenotype and HIF-1α expression in human colon cancer cells. Cancer medicine 22 24634093
2021 Urine LOX-1 and Volatilome as Promising Tools towards the Early Detection of Renal Cancer. Cancers 21 34439368
2020 Immunological Outcomes Mediated Upon Binding of Heat Shock Proteins to Scavenger Receptors SCARF1 and LOX-1, and Endocytosis by Mononuclear Phagocytes. Frontiers in immunology 21 31998315
2020 LOX-1 Regulates P. gingivalis-Induced Monocyte Migration and Adhesion to Human Umbilical Vein Endothelial Cells. Frontiers in cell and developmental biology 21 32793587
2017 LOX-1 promotes right ventricular hypertrophy in hypoxia-exposed rats. Life sciences 21 28259654
2024 LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review. International journal of molecular sciences 20 38791315
2017 LOX-1 is involved in IL-1β production and extracellular matrix breakdown in dental peri-implantitis. International immunopharmacology 20 28898769
2016 Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques. PloS one 20 27077384
2015 LOX-1 in macrophage migration in response to ox-LDL and the involvement of calpains. Biochemical and biophysical research communications 20 26393906
2015 The human rs1050286 polymorphism alters LOX-1 expression through modifying miR-24 binding. Journal of cellular and molecular medicine 20 26542080
2013 OLR1, PON1 and MTHFR gene polymorphisms, conventional risk factors and the severity of coronary atherosclerosis in a Chinese Han population. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 23391848
2011 LOX-1/LOXIN: the yin/yang of atheroscleorosis. Cardiovascular drugs and therapy 20 21904818
2023 Expression of OLR1 gene on tumor-associated macrophages of head and neck squamous cell carcinoma, and its correlation with clinical outcome. Oncoimmunology 19 37089448
2021 Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1. Frontiers in cardiovascular medicine 19 33553253
2013 LOX-1: a male hormone-regulated scavenger receptor for atherosclerosis. Vascular pharmacology 19 24157503
2011 LOX-1: a critical player in the genesis and progression of myocardial ischemia. Cardiovascular drugs and therapy 19 21847544
2024 LOX-1 acts as an N6-methyladenosine-regulated receptor for Helicobacter pylori by binding to the bacterial catalase. Nature communications 18 38253620
2024 Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification. Molecular medicine (Cambridge, Mass.) 18 39123116
2013 LOX-1 in the maintenance of cytoskeleton and proliferation in senescent cardiac fibroblasts. Journal of molecular and cellular cardiology 18 23648807

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