GO:0150024 oxidised low-density lipoprotein particle clearance: Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0150024 describes the receptor-mediated removal of oxidised low-density lipoprotein (oxLDL) particles from the blood and the degradation of their constituent parts.
• OxLDL clearance is a major homeostatic process that prevents the accumulation of pro-inflammatory and pro-atherogenic lipoprotein particles in the circulation.
• Scavenger receptors such as LOX-1, CD36, and SR-A recognise oxidised phospholipids and apolipoprotein B modifications on oxLDL, driving its internalisation.
• Impaired oxLDL clearance contributes to atherosclerosis, familial hypercholesterolemia, and other cardiovascular disorders.
• The process is regulated by plasma factors, including heparin-sensitive pathways and PCSK9-mediated LDL receptor modulation.
• Experimental models for studying GO:0150024 include knockout and transgenic mice, cell-based receptor assays, and nanomedicine-based targeting strategies.
Description
Oxidised low-density lipoprotein particle clearance (GO:0150024) is the biological process by which oxidised low-density lipoprotein (oxLDL) particles are removed from the bloodstream via receptor-mediated endocytosis and subsequently degraded. This process is essential for maintaining lipid homeostasis and preventing the accumulation of oxidatively modified lipoproteins that drive vascular inflammation and atherosclerosis. Unlike native LDL, which is primarily cleared by the hepatic LDL receptor, oxLDL is recognised by a distinct set of scavenger receptors on macrophages and endothelial cells, making its clearance a unique and critical arm of lipoprotein metabolism. Researchers study GO:0150024 because its dysregulation is directly linked to cardiovascular disease. Elevated plasma oxLDL levels are observed in familial hypercholesterolemia and are associated with increased atherosclerotic burden. Therapeutic interventions such as statins and PCSK9 inhibitors can modulate oxLDL clearance and reduce circulating oxidised lipids. Understanding the molecular players and regulatory mechanisms of oxLDL clearance is therefore central to developing targeted therapies for atherosclerosis and related metabolic disorders. This article provides a comprehensive overview of GO:0150024, covering its definition, the genes and proteins involved, its role in disease, and the experimental methods used to study it. All statements are grounded in published literature to support research-grade accuracy [1-8].
oxidised low-density lipoprotein particle clearance At A Glance
| GO ID | GO:0150024 |
|---|---|
| GO term | oxidised low-density lipoprotein particle clearance |
| Ontology | biological_process |
| Synonym | oxidised LDL particle clearance; oxidized LDL particle clearance; oxidized low-density lipoprotein particle clearance; ox-LDL particle clearance; oxLDL particle clearance |
| Major function | Receptor-mediated removal of oxidised LDL particles from the blood and degradation of their constituent parts |
| Cellular location | Plasma membrane, endosomes, lysosomes |
| Key receptors | LOX-1, CD36, SR-A, LDLR |
| Associated diseases | Atherosclerosis, familial hypercholesterolemia, dyslipidemia |
| Regulatory factors | PCSK9, heparin-sensitive pathways, statins |
What Is GO:0150024?
GO:0150024, oxidised low-density lipoprotein particle clearance, is defined as the process in which an oxidised low-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts are degraded. This process involves the recognition of oxidised LDL by specific cell-surface receptors, internalisation into endosomes, and subsequent lysosomal degradation of the particle's lipid and protein components.
Why Is oxidised low-density lipoprotein particle clearance Important in Cell Biology?
GO:0150024 is critically important because it governs the removal of oxidised LDL, a major driver of atherosclerosis and cardiovascular disease. Impaired clearance leads to the accumulation of oxLDL in the circulation and arterial wall, promoting foam cell formation, inflammation, and plaque development. Understanding this process provides insights into disease mechanisms and therapeutic targets, including statins, PCSK9 inhibitors, and nanomedicine-based approaches.
• Prevents accumulation of pro-inflammatory oxidised LDL in the bloodstream.
• Protects against atherosclerosis by reducing foam cell formation.
• Dysregulation is linked to familial hypercholesterolemia and dyslipidemia.
• Serves as a target for lipid-lowering therapies such as statins and PCSK9 inhibitors.
• Involved in postprandial lipoprotein metabolism and vascular homeostasis.
• Heparin-sensitive pathways modulate oxLDL clearance, affecting plasma retention.
• Nanomedicine strategies targeting lesional macrophages aim to restore cholesterol homeostasis.
• Provides a model for studying receptor-mediated endocytosis and lysosomal degradation.
• Biomarker potential for cardiovascular risk assessment.
• Relevant to immune responses against oxidised LDL in chronic inflammation.
What Happens During oxidised low-density lipoprotein particle clearance?
Recognition and Binding of Oxidised LDL
In simple terms: The body tags oxidised LDL particles for removal by recognising them with special receptors on cells.
Oxidised LDL particles are recognised by scavenger receptors such as LOX-1, CD36, and SR-A on macrophages and endothelial cells. These receptors bind to oxidised phospholipids and modified apolipoprotein B-100 on the particle surface, initiating the clearance process. This recognition is a key step that distinguishes oxLDL from native LDL, which is primarily cleared by the LDL receptor.
Receptor-Mediated Endocytosis
In simple terms: Once bound, the cell engulfs the oxidised LDL particle, pulling it inside.
Following receptor binding, oxLDL is internalised via receptor-mediated endocytosis, forming endocytic vesicles that deliver the particle to endosomes. This process is dependent on clathrin-coated pits and dynamin, and it requires functional receptor recycling. The internalisation rate can be modulated by factors such as PCSK9, which affects LDL receptor availability.
Intracellular Trafficking and Degradation
In simple terms: Inside the cell, the oxidised LDL is broken down in lysosomes into its basic components.
After endocytosis, oxLDL particles are trafficked to lysosomes where acidic hydrolases degrade the oxidised lipids and proteins into free cholesterol, fatty acids, and amino acids. This degradation step is essential for preventing the accumulation of toxic oxidised lipids and for recycling cellular components. Impaired lysosomal degradation can lead to cholesterol crystal formation and inflammasome activation.
Regulation by Plasma Factors and Heparin
In simple terms: Substances in the blood, like heparin, can influence how quickly oxidised LDL is cleared.
The clearance of oxidised LDL from plasma is influenced by heparin-sensitive pathways. Injection of heparin prolongs the plasma clearance of oxidised LDL in rats, suggesting that heparin competes with receptor binding or alters lipoprotein lipase-mediated uptake. This highlights the role of plasma factors in modulating GO:0150024.
Impact of Statins and PCSK9 Inhibition
In simple terms: Cholesterol-lowering drugs can enhance the removal of oxidised LDL from the blood.
Statins and PCSK9 inhibitors have been shown to affect oxLDL clearance. PCSK9 inhibition reduces plasma levels of small dense LDL-cholesterol and 7-ketocholesterol, an oxidised sterol. Statins combined with AAV8-TBG-LOX-1 reduce vascular lipid-driven inflammatory responses and inhibit atherosclerosis, partly by enhancing oxLDL clearance pathways. These interventions demonstrate that GO:0150024 is pharmacologically modifiable.
Key Genes Involved in GO:0150024 oxidised low-density lipoprotein particle clearance
The following genes and proteins are central to the recognition, internalisation, and degradation of oxidised LDL particles in GO:0150024.
| Gene | Major Role | Research Relevance |
|---|---|---|
| OLR1 (LOX-1) | Scavenger receptor for oxidised LDL; mediates binding and internalisation | Target for atherosclerosis therapy; studied in endothelial cells and macrophages |
| CD36 | Scavenger receptor recognising oxidised phospholipids; facilitates oxLDL uptake | Linked to foam cell formation; knockout models reduce atherosclerosis |
| MSR1 (SR-A) | Scavenger receptor mediating oxLDL endocytosis in macrophages | Genetic variants associated with cardiovascular risk |
| LDLR | Native LDL receptor; indirectly affects oxLDL clearance via plasma lipid levels | Mutations cause familial hypercholesterolemia; target of statins and PCSK9 inhibitors |
| PCSK9 | Regulates LDL receptor degradation; influences oxLDL clearance indirectly | Therapeutic target; inhibitors reduce oxidised lipids |
| APOB | Structural apolipoprotein of LDL; modifications trigger scavenger receptor recognition | Oxidised APOB epitopes are biomarkers |
| APOE | Lipoprotein involved in cholesterol transport; modulates oxLDL clearance | Isoform-specific effects on atherosclerosis |
| LPL | Lipoprotein lipase; heparin-sensitive enzyme affecting oxLDL clearance | Heparin injection prolongs oxLDL clearance in rats |
| SCARB1 (SR-BI) | HDL receptor; may influence oxLDL clearance indirectly | Studied in reverse cholesterol transport |
| ABCA1 | Cholesterol efflux pump; affects cellular cholesterol homeostasis | Mutations cause Tangier disease; linked to oxLDL handling |
| ABCG1 | Cholesterol efflux transporter; modulates macrophage cholesterol | Relevant to foam cell formation |
| NR1H3 (LXR) | Nuclear receptor regulating cholesterol efflux genes | Target for enhancing oxLDL clearance |
| PPARG | Nuclear receptor controlling macrophage lipid metabolism | Agonists affect oxLDL uptake |
| TNF | Pro-inflammatory cytokine induced by oxLDL | Biomarker of oxLDL-mediated inflammation |
| IL6 | Cytokine involved in oxLDL-induced inflammation | Linked to atherosclerosis progression |
| CXCL1 | Chemokine mediating monocyte recruitment in response to oxLDL | Studied in vascular inflammation |
| MMP9 | Matrix metalloproteinase activated by oxLDL | Contributes to plaque instability |
| HMOX1 | Heme oxygenase-1; antioxidant enzyme induced by oxLDL | Protective role in oxLDL clearance |
How Is oxidised low-density lipoprotein particle clearance Regulated?
GO:0150024 is regulated at multiple levels. Plasma factors such as heparin can prolong oxLDL clearance by interfering with receptor binding or lipoprotein lipase activity. PCSK9 modulates LDL receptor availability, indirectly affecting oxLDL clearance, and its inhibition reduces oxidised lipid levels. Statins enhance oxLDL clearance pathways and reduce vascular inflammation. Additionally, nuclear receptors such as LXR and PPARγ regulate the expression of scavenger receptors and cholesterol efflux transporters, thereby influencing oxLDL uptake and degradation.
oxidised low-density lipoprotein particle clearance and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| OLR1 (LOX-1) | Atherosclerosis | LOX-1 knockout mice; endothelial cell-specific overexpression |
| LDLR | Familial hypercholesterolemia | LDLR knockout mice; AAV-mediated gene delivery |
| PCSK9 | Hypercholesterolemia | PCSK9 gain-of-function transgenic mice; inhibitor studies |
| CD36 | Atherosclerosis and insulin resistance | CD36 knockout mice; macrophage-specific deletion |
| APOE | Atherosclerosis | ApoE knockout mice; human APOE isoform knock-in |
Atherosclerosis and Cardiovascular Disease
Impaired clearance of oxidised LDL is a hallmark of atherosclerosis. OxLDL accumulates in the arterial intima, where it is taken up by macrophages via scavenger receptors, leading to foam cell formation and plaque development. Elevated plasma oxLDL levels correlate with increased cardiovascular risk, and therapeutic strategies aimed at enhancing clearance, such as statins and PCSK9 inhibitors, reduce atherosclerotic burden.
Familial Hypercholesterolemia
Children with familial hypercholesterolemia exhibit elevated oxidised LDL levels, which can be reduced by pravastatin treatment. This indicates that defective LDL receptor function not only increases native LDL but also contributes to oxLDL accumulation, underscoring the clinical relevance of GO:0150024 in inherited dyslipidemias.
Dyslipidemia and Postprandial Lipemia
Dyslipidemia, characterized by abnormal lipid profiles, is associated with impaired oxLDL clearance. Postprandial lipoproteins and their remnants can modulate vascular homeostasis and influence oxLDL clearance pathways, linking dietary fat intake to cardiovascular risk.
Inflammation and Immune Responses
Oxidised LDL elicits immunological responses, including the production of autoantibodies and activation of inflammatory cytokines. These immune reactions can further impair clearance and exacerbate vascular damage, creating a vicious cycle in chronic inflammatory diseases.
From oxidised low-density lipoprotein particle clearance-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate oxLDL clearance in vivo? | Knockout mouse model (e.g., OLR1-/-) with oxLDL injection and plasma clearance assay |
| Does a specific point mutation in LDLR affect oxLDL uptake? | Point-mutation knock-in mice or cell lines expressing mutant LDLR |
| Can overexpression of LOX-1 enhance oxLDL clearance? | Transgenic mice overexpressing LOX-1 in macrophages or endothelial cells |
| What is the role of PCSK9 in oxLDL clearance? | PCSK9 knockout or gain-of-function models; pharmacological inhibition |
| How does heparin affect oxLDL clearance? | Rat model with heparin injection and plasma clearance measurement |
| Can nanomedicine target lesional macrophages to improve oxLDL clearance? | ApoE-/- mice treated with macrophage-targeted nanoparticles |
How to Study the oxidised low-density lipoprotein particle clearance Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabelled oxLDL clearance | Plasma disappearance of oxLDL | In vivo pharmacokinetics in rodents |
| Flow cytometry | Cellular uptake of fluorescent oxLDL | Macrophage scavenger receptor activity |
| Confocal microscopy | Intracellular trafficking and degradation | Localisation of oxLDL in endosomes/lysosomes |
| RNA-seq | Transcriptional changes during oxLDL clearance | Identifying regulatory genes |
| Proteomics | Protein expression and modifications | Discovering novel receptors or enzymes |
| Lipidomics (LC-MS) | Oxidised lipid species (e.g., 7-ketocholesterol) | Biomarker of oxLDL clearance |
| ELISA | Plasma oxLDL levels | Clinical studies and animal models |
| Immunohistochemistry | Tissue localisation of oxLDL and receptors | Atherosclerotic plaque analysis |
In Vivo Clearance Assays
Plasma clearance of oxidised LDL can be measured by injecting radiolabelled or fluorescently labelled oxLDL into animal models and monitoring its disappearance from the bloodstream over time. This method has been used to show that heparin prolongs oxLDL clearance in rats.
Cellular Uptake and Degradation Assays
Cultured macrophages or endothelial cells can be incubated with labelled oxLDL to measure receptor-mediated endocytosis and lysosomal degradation. Flow cytometry and confocal microscopy are used to quantify internalisation and intracellular trafficking.
Gene Expression and Proteomics
RNA-seq and proteomics can identify genes and proteins differentially expressed during oxLDL clearance, revealing novel regulators. For example, statin treatment alters the expression of cholesterol homeostasis genes.
Lipidomic and Oxysterol Analysis
Mass spectrometry-based lipidomics quantifies oxidised lipids such as 7-ketocholesterol, a marker of oxLDL clearance efficiency. PCSK9 inhibition reduces plasma 7-ketocholesterol levels, demonstrating the utility of this method.
How CRISPR Can Be Used to Study GO:0150024 oxidised low-density lipoprotein particle clearance
Knockout
CRISPR knockout of genes such as OLR1, CD36, or MSR1 in cell lines or mice can abolish oxLDL clearance, providing direct evidence of their necessity. EDITGENE offers custom knockout models to study GO:0150024.
Point Mutation
Introducing point mutations in LDLR or PCSK9 that mimic human variants can reveal how specific amino acid changes affect oxLDL clearance. EDITGENE provides precision point-mutation cell models.
Knock-in
Knock-in of human APOE isoforms or tagged receptors (e.g., LOX-1-GFP) allows tracking of oxLDL clearance in live cells and tissues. EDITGENE offers knock-in services for such studies.
Overexpression
Overexpression of scavenger receptors like LOX-1 or CD36 can enhance oxLDL clearance and reduce atherosclerosis in mouse models. EDITGENE provides overexpression cell models and AAV-based delivery.
How EDITGENE Supports oxidised low-density lipoprotein particle clearance Research
Researchers studying oxidised low-density lipoprotein particle clearance-related genes often need to determine whether a candidate gene is causally involved in oxLDL uptake, degradation, or regulation. CRISPR-based models provide a robust way to test gene function in relevant cell types and animal models.
Contact EDITGENE today to design your custom CRISPR model for oxidised low-density lipoprotein particle clearance research.
Frequently Asked Questions About oxidised low-density lipoprotein particle clearance
What is GO:0150024?
GO:0150024 is the Gene Ontology term for oxidised low-density lipoprotein particle clearance, the process by which oxidised LDL is removed from the blood via receptor-mediated endocytosis and degraded.
What genes are involved in oxidised LDL clearance?
Key genes include OLR1 (LOX-1), CD36, MSR1, LDLR, PCSK9, and APOB, among others.
How is oxidised LDL cleared from the blood?
Oxidised LDL is recognised by scavenger receptors on macrophages and endothelial cells, internalised via endocytosis, and degraded in lysosomes.
Why is oxidised LDL clearance important?
It prevents the accumulation of pro-inflammatory oxidised LDL, which drives atherosclerosis and cardiovascular disease.
What diseases are associated with impaired oxidised LDL clearance?
Atherosclerosis, familial hypercholesterolemia, and dyslipidemia are linked to defective oxLDL clearance.
How do statins affect oxidised LDL clearance?
Statins can enhance oxLDL clearance pathways and reduce vascular inflammation, partly by improving cholesterol homeostasis.
Does PCSK9 inhibition affect oxidised LDL?
Yes, PCSK9 inhibition reduces plasma levels of small dense LDL-cholesterol and 7-ketocholesterol, an oxidised sterol.
What models are used to study oxidised LDL clearance?
Common models include knockout mice (e.g., OLR1-/-, CD36-/-), cell-based uptake assays, and nanomedicine-targeted approaches.
How does heparin influence oxidised LDL clearance?
Heparin injection prolongs the plasma clearance of oxidised LDL in rats, likely by interfering with receptor binding or lipoprotein lipase.
Can CRISPR be used to study oxidised LDL clearance?
Yes, CRISPR knockout, knock-in, and overexpression models are powerful tools to dissect gene function in oxLDL clearance.
Conclusion
GO:0150024, oxidised low-density lipoprotein particle clearance, is a vital biological process that protects against atherosclerosis by removing pro-inflammatory oxidised LDL from the circulation. Its dysregulation contributes to cardiovascular diseases, making it a key target for therapeutic intervention. Advances in CRISPR gene editing and nanomedicine are providing new ways to study and modulate this process, offering hope for improved treatments.
References
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- 2. Koba S et al.. 2011. [Dyslipidemia and atherosclerosis].. Nihon Rinsho 69(1):138-43 PMID: 21226274
- 3. Mahmood T et al.. 2024. Effect of PCSK9 inhibition on plasma levels of small dense low density lipoprotein-cholesterol and 7-ketocholesterol.. J Clin Lipidol 18(1):e50-e58 PMID: 37923663
- 4. Hörkkö S et al.. 2000. Immunological responses to oxidized LDL.. Free Radic Biol Med 28(12):1771-9 PMID: 10946219
- 5. Botham KM et al.. 2013. Postprandial lipoproteins and the molecular regulation of vascular homeostasis.. Prog Lipid Res 52(4):446-64 PMID: 23774609
- 6. Rodenburg J et al.. 2006. Oxidized low-density lipoprotein in children with familial hypercholesterolemia and unaffected siblings: effect of pravastatin.. J Am Coll Cardiol 47(9):1803-10 PMID: 16682304
- 7. Zhou WP et al.. 2024. Statins Combined with AAV8-TBG-LOX-1 Reduce the Vascular Lipid-driven Inflammatory Response and Inhibit Atherosclerosis.. Curr Med Sci 44(6):1097-1102 PMID: 39627476
- 8. Wunder A et al.. 1995. The injection of heparin prolongs the plasma clearance of oxidized low density lipoprotein in the rat.. Thromb Res 78(2):139-49 PMID: 7482431
