GO:0150025 oxidised low-density lipoprotein particle receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0150025 describes the molecular function of binding an oxidised low-density lipoprotein (oxLDL) particle and delivering it into the cell via endocytosis.
• The best-characterised receptor carrying this activity is LOX-1 (OLR1), a lectin-like scavenger receptor that binds oxLDL and drives endothelial dysfunction and atherosclerosis.
• CD36 is another major scavenger receptor for oxLDL and contributes to foam cell formation and inflammatory signalling in atherosclerosis.
• oxLDL is not a single molecule; it carries oxidised phospholipids and PAF-like lipids that activate platelets and inflammatory pathways.
• oxLDL uptake via this activity promotes PKM2-mediated mitochondrial reactive oxygen species (mtROS) production and phagocytosis.
• Pharmacological disruption of membrane rafts with cholesterol-lowering drugs can inhibit LOX-1 receptor function, linking this activity to therapeutic modulation.
Description
GO:0150025, oxidised low-density lipoprotein particle receptor activity, is a molecular function term that defines the binding of an oxidised low-density lipoprotein (oxLDL) particle and its delivery into the cell via endocytosis. This activity is central to lipid handling by vascular and immune cells and is a key driver of atherosclerotic plaque development. Unlike the classical LDL receptor, which recognises native apolipoprotein B-100, oxLDL receptors recognise oxidatively modified lipid and protein epitopes generated during oxidative stress. The best-characterised receptor for this activity is LOX-1 (encoded by OLR1), a lectin-like scavenger receptor expressed on endothelial cells, macrophages, and smooth muscle cells. CD36 is another major scavenger receptor that binds oxLDL and contributes to foam cell formation. Because oxLDL uptake is mechanistically linked to inflammation, platelet activation, and mitochondrial stress, researchers study this activity to understand cardiovascular disease, metabolic disorders, and potential therapeutic targets.
oxidised low-density lipoprotein particle receptor activity At A Glance
| GO ID | GO:0150025 |
|---|---|
| GO term | oxidised low-density lipoprotein particle receptor activity |
| Ontology | molecular_function |
| Synonym | oxidised LDL receptor activity; oxidized LDL receptor activity; ox-LDL receptor activity; oxLDL receptor activity; LOX-1 receptor activity |
| Major function | Binding oxidised low-density lipoprotein particles and delivering them into the cell via endocytosis |
| Major receptors | LOX-1 (OLR1), CD36, and other scavenger receptors |
| Ligand | Oxidised low-density lipoprotein (oxLDL) particles containing oxidised phospholipids and PAF-like lipids |
| Downstream effects | Inflammatory signalling, foam cell formation, mtROS production, phagocytosis |
| Therapeutic relevance | Target for cholesterol-lowering drugs that disrupt membrane rafts |
What Is GO:0150025?
In our own words, GO:0150025 describes a receptor's ability to recognise and bind an oxidised low-density lipoprotein particle and then internalise that particle through endocytosis. This is a molecular function: it specifies what the receptor does at the biochemical level, not the downstream cellular process. The term covers receptors such as LOX-1 and CD36 that bind oxidatively modified LDL and deliver it into the cell, distinguishing this activity from native LDL receptor activity.
Why Is oxidised low-density lipoprotein particle receptor activity Important in Cell Biology?
GO:0150025 is important because oxLDL uptake through this receptor activity is a primary mechanism linking oxidative stress to atherosclerosis, thrombosis, and metabolic inflammation. LOX-1 and CD36, the principal receptors carrying this activity, are expressed on endothelial cells, macrophages, and platelets, where they mediate pro-inflammatory and pro-thrombotic responses. Understanding this activity helps researchers design interventions that block pathological oxLDL uptake without disrupting normal lipid metabolism.
• Drives endothelial dysfunction and atherosclerotic plaque formation through oxLDL uptake.
• Mediates foam cell formation in macrophages via CD36 and LOX-1.
• Activates platelets and contributes to thrombotic risk.
• Stimulates PKM2-mediated mitochondrial reactive oxygen species production and phagocytosis.
• Provides a therapeutic target for cholesterol-lowering drugs that disrupt membrane rafts.
• Links oxidative stress to inflammatory signalling via oxidised phospholipids and PAF-like lipids.
• Serves as a biomarker and mechanistic node in cardiovascular risk assessment.
• Enables study of scavenger receptor structure-function relationships.
Molecular Mechanism of oxidised low-density lipoprotein particle receptor activity
Ligand recognition and binding
In simple terms: The receptor grabs onto oxidised LDL particles floating outside the cell.
LOX-1 recognises oxidised low-density lipoprotein particles through its lectin-like domain, which binds oxidised phospholipid and protein epitopes generated during LDL oxidation. CD36 also binds oxLDL via distinct structural determinants. This binding is the first step of GO:0150025 and is independent of the classical LDL receptor pathway.
Endocytic uptake and internalisation
In simple terms: After grabbing oxLDL, the receptor pulls it inside the cell.
Following binding, the receptor-oxLDL complex is internalised via endocytosis, delivering the oxidised lipoprotein particle into the endosomal compartment. This endocytic delivery is the defining feature of GO:0150025 and distinguishes it from simple ligand sequestration.
Membrane raft localisation and regulation
In simple terms: The receptor sits in special membrane patches that can be disrupted by drugs.
LOX-1 function depends on localisation in membrane rafts; cholesterol-lowering drugs that disrupt these rafts inhibit LOX-1 receptor function, providing a pharmacological handle on this activity. This raft dependence links membrane lipid composition to oxLDL uptake efficiency.
Downstream signalling and metabolic consequences
In simple terms: Once oxLDL is inside, it triggers stress and inflammation.
oxLDL internalised through this activity stimulates PKM2-mediated mitochondrial reactive oxygen species production and enhances phagocytosis. It also delivers inflammatory PAF-like phospholipids that activate platelets and vascular cells. These downstream events connect GO:0150025 to atherosclerosis and thrombosis.
Key Genes Involved in GO:0150025 oxidised low-density lipoprotein particle receptor activity
The following genes encode receptors, ligands, and signalling proteins directly implicated in oxidised low-density lipoprotein particle receptor activity and its downstream biology.
| Gene | Major Role | Research Relevance |
|---|---|---|
| OLR1 (LOX-1) | Primary lectin-like receptor for oxLDL; mediates binding and endocytosis | Knockout and overexpression models for atherosclerosis and endothelial dysfunction |
| CD36 | Scavenger receptor that binds oxLDL and drives foam cell formation | Target for metabolic and cardiovascular studies |
| SCARB1 (SR-BI) | Scavenger receptor involved in lipoprotein uptake | Studied in lipid metabolism and atherosclerosis |
| PKM2 | Pyruvate kinase M2; mediates mtROS production downstream of oxLDL | Metabolic and oxidative stress research |
| APOE | Apolipoprotein E; modulates lipoprotein clearance and atherosclerosis risk | Mouse models of atherosclerosis |
| LDLR | Classical LDL receptor; contrasts with oxLDL receptor activity | Familial hypercholesterolemia models |
| PLA2G7 | Lipoprotein-associated phospholipase A2; generates oxidised phospholipids | Inflammatory lipid mediator studies |
| PAFAH | Platelet-activating factor acetylhydrolase; regulates PAF-like lipids | Platelet and inflammation research |
| TNF | Pro-inflammatory cytokine induced by oxLDL signalling | Inflammation and atherosclerosis models |
| IL6 | Cytokine upregulated in oxLDL-stimulated cells | Vascular inflammation studies |
| NFKB1 | Transcription factor activated by oxLDL receptor signalling | Inflammatory pathway research |
| MAPK1 | Kinase involved in oxLDL-induced signalling | Signal transduction studies |
| SRC | Kinase implicated in scavenger receptor signalling | Phagocytosis and cytoskeletal studies |
| RAC1 | Small GTPase involved in phagocytic uptake | Cytoskeleton and endocytosis research |
| ABCA1 | Cholesterol efflux transporter counterbalancing oxLDL uptake | Reverse cholesterol transport studies |
| ABCG1 | Cholesterol efflux transporter in macrophages | Foam cell formation research |
| CXCL1 | Chemokine induced by oxLDL in vascular cells | Leukocyte recruitment studies |
| VCAM1 | Adhesion molecule upregulated by oxLDL | Endothelial activation research |
How Is oxidised low-density lipoprotein particle receptor activity Regulated?
The activity of oxidised low-density lipoprotein particle receptors is regulated at multiple levels. Membrane raft integrity is critical for LOX-1 function, and cholesterol-lowering drugs that disrupt rafts inhibit receptor activity. Inflammatory cytokines and oxidative stress can upregulate receptor expression, creating a feed-forward loop that amplifies oxLDL uptake. Downstream, PKM2-mediated mitochondrial reactive oxygen species production can further modulate cellular responses to oxLDL. Additionally, the lipid composition of oxLDL particles, including oxidised phospholipids and PAF-like lipids, influences receptor engagement and downstream signalling.
oxidised low-density lipoprotein particle receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| OLR1 (LOX-1) | Atherosclerosis, endothelial dysfunction | Knockout and overexpression in endothelial cells and ApoE-/- mice |
| CD36 | Atherosclerosis, foam cell formation | Macrophage-specific knockout and lipid uptake assays |
| PKM2 | Metabolic stress, mtROS production | Knockdown and pharmacological inhibition in macrophages |
| APOE | Cardiovascular risk, lipid metabolism | ApoE-/- mouse models and human genetic studies |
| PLA2G7 | Inflammatory lipid signalling | Enzyme activity assays and knockout models |
Atherosclerosis and cardiovascular disease
Oxidised low-density lipoprotein particle receptor activity is a central mechanism in atherogenesis. LOX-1 and CD36 mediate oxLDL uptake by endothelial cells and macrophages, leading to foam cell formation, endothelial dysfunction, and plaque development. Elevated oxLDL levels are associated with increased cardiovascular risk, and this receptor activity is a therapeutic target for cholesterol-lowering strategies.
Thrombosis and platelet activation
oxLDL contains inflammatory PAF-like phospholipids that activate platelets, and receptor-mediated uptake contributes to pro-thrombotic states. Platelets interact with oxLDL, and this activity may amplify thrombotic risk in patients with dyslipidemia.
Metabolic and inflammatory disorders
Beyond atherosclerosis, oxLDL receptor activity stimulates PKM2-mediated mitochondrial reactive oxygen species production and phagocytosis, linking it to metabolic reprogramming and innate immune activation. This has implications for diabetes, obesity, and chronic inflammatory diseases.
From oxidised low-density lipoprotein particle receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does OLR1 mediate oxLDL uptake in endothelial cells? | OLR1 knockout endothelial cell line |
| What is the role of CD36 in foam cell formation? | CD36 knockout macrophages |
| Does PKM2 link oxLDL uptake to mtROS? | PKM2 knockdown or point-mutation macrophages |
| Can membrane raft disruption inhibit LOX-1 function? | LOX-1 overexpression with cholesterol-lowering drug treatment |
| What is the effect of oxLDL on platelet activation? | Platelet-rich plasma with oxLDL stimulation |
| Does APOE modulate oxLDL receptor activity in vivo? | ApoE-/- mouse model |
How to Study the oxidised low-density lipoprotein particle receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| DiI-oxLDL uptake assay | Receptor-mediated internalisation of oxLDL | Screening candidate receptors and inhibitors |
| CRISPR knockout | Loss-of-function effects on oxLDL uptake | Validating OLR1 and CD36 as receptors |
| Western blot | Protein expression and signalling changes | Measuring NF-kB, MAPK activation |
| Seahorse assay | Mitochondrial respiration and mtROS | Assessing metabolic impact of oxLDL |
| Confocal microscopy | Receptor localisation and raft association | Studying membrane raft disruption |
| Platelet aggregation assay | Thrombotic response to oxLDL | Evaluating PAF-like lipid effects |
| ELISA | Cytokine and chemokine secretion | Quantifying inflammatory response |
| Flow cytometry | Cell surface receptor levels and oxLDL binding | Phenotyping macrophages and endothelial cells |
Ligand binding and uptake assays
Fluorescently labelled oxLDL (e.g., DiI-oxLDL) is used to measure binding and internalisation in cells expressing candidate receptors. This directly quantifies GO:0150025 activity.
Genetic knockout and knockdown
CRISPR knockout or siRNA knockdown of OLR1, CD36, or other candidate genes followed by oxLDL uptake assays identifies which receptors carry this activity.
Signalling and metabolic readouts
Western blotting, phospho-kinase arrays, and Seahorse assays measure downstream signalling and metabolic changes, such as PKM2-mediated mtROS production, after oxLDL stimulation.
Imaging and membrane raft analysis
Confocal microscopy and membrane raft fractionation assess receptor localisation and raft dependence, which is critical for LOX-1 function.
How CRISPR Can Be Used to Study GO:0150025 oxidised low-density lipoprotein particle receptor activity
Knockout
CRISPR knockout of OLR1 or CD36 in endothelial cells or macrophages abolishes oxLDL uptake, confirming their role in GO:0150025. Knockout models are essential for distinguishing receptor-specific contributions to atherosclerosis.
Point Mutation
Point mutations in the ligand-binding domain of LOX-1 or CD36 can dissect residues required for oxLDL recognition versus endocytic delivery. Such models help define the molecular determinants of GO:0150025.
Knock-in
Knock-in of tagged receptors (e.g., GFP-LOX-1) enables live-cell imaging of oxLDL uptake and trafficking. Knock-in of human variants into mouse models can test disease-associated alleles.
Overexpression
Overexpression of OLR1 or CD36 in cell lines enhances oxLDL uptake and downstream signalling, providing a gain-of-function system to study GO:0150025 and test inhibitors.
How EDITGENE Supports oxidised low-density lipoprotein particle receptor activity Research
Researchers studying oxidised low-density lipoprotein particle receptor activity-related genes often need to determine whether a candidate gene is causally involved in oxLDL binding, uptake, or downstream signalling. EDITGENE provides CRISPR-based cell model services to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for oxidised low-density lipoprotein particle receptor activity research.
Frequently Asked Questions About oxidised low-density lipoprotein particle receptor activity
What is oxidised low-density lipoprotein particle receptor activity?
It is a molecular function (GO:0150025) where a receptor binds an oxidised LDL particle and delivers it into the cell via endocytosis.
What genes are involved in oxidised low-density lipoprotein particle receptor activity?
Key genes include OLR1 (LOX-1), CD36, SCARB1, and downstream effectors such as PKM2.
What is the role of LOX-1 in oxLDL uptake?
LOX-1 is a lectin-like receptor that binds oxLDL and mediates its endocytic uptake, contributing to endothelial dysfunction and atherosclerosis.
How is oxidised LDL different from native LDL?
Oxidised LDL carries oxidised phospholipids and PAF-like lipids that are recognised by scavenger receptors rather than the classical LDL receptor.
What diseases are linked to oxidised LDL receptor activity?
Atherosclerosis, thrombosis, and metabolic inflammatory disorders are linked to this activity.
Can drugs inhibit oxidised LDL receptor activity?
Cholesterol-lowering drugs that disrupt membrane rafts can inhibit LOX-1 receptor function.
What methods are used to study oxidised LDL receptor activity?
DiI-oxLDL uptake assays, CRISPR knockout, Western blotting, and imaging are commonly used.
What is the role of CD36 in atherosclerosis?
CD36 mediates oxLDL uptake in macrophages, leading to foam cell formation and plaque development.
How does oxLDL affect mitochondria?
oxLDL stimulates PKM2-mediated mitochondrial reactive oxygen species production and phagocytosis.
What CRISPR models are available for oxLDL receptor research?
Knockout, point mutation, knock-in, and overexpression models for OLR1, CD36, and related genes.
Conclusion
GO:0150025, oxidised low-density lipoprotein particle receptor activity, is a critical molecular function linking oxidative lipid modifications to cellular uptake and inflammatory signalling. Receptors such as LOX-1 and CD36 mediate this activity and are central to atherosclerosis, thrombosis, and metabolic disease. Continued research using CRISPR models and functional assays will clarify how this activity can be therapeutically modulated.
References
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- 2. Relou IA et al.. 2003. Low-density lipoprotein and its effect on human blood platelets.. Cell Mol Life Sci 60(5):961-71 PMID: 12827283
- 3. Dunn S et al.. 2008. The lectin-like oxidized low-density-lipoprotein receptor: a pro-inflammatory factor in vascular disease.. Biochem J 409(2):349-55 PMID: 18092947
- 4. Zeya B et al.. 2019. LOX-1: Its cytotopographical variance and disease stress.. J Biochem Mol Toxicol 33(9):e22375 PMID: 31332899
- 5. Zhang J et al.. 2025. Oxidized LDL stimulates PKM2-mediated mtROS production and phagocytosis.. J Lipid Res 66(5):100809 PMID: 40250804
- 6. Matarazzo S et al.. 2012. Cholesterol-lowering drugs inhibit lectin-like oxidized low-density lipoprotein-1 receptor function by membrane raft disruption.. Mol Pharmacol 82(2):246-54 PMID: 22570368
- 7. Tian K et al.. 2020. CD36 in Atherosclerosis: Pathophysiological Mechanisms and Therapeutic Implications.. Curr Atheroscler Rep 22(10):59 PMID: 32772254
- 8. Marathe GK et al.. 2001. Oxidized LDL contains inflammatory PAF-like phospholipids.. Trends Cardiovasc Med 11(3-4):139-42 PMID: 11686003
