GO:0140052 cellular response to oxidised low-density lipoprotein particle stimulus: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0140052 describes how a cell changes its state or activity in response to oxidised low-density lipoprotein (oxLDL) particles.
• oxLDL triggers rapid transcriptomic reprogramming in human vascular smooth muscle cells, affecting hundreds of genes within hours.
• The response includes inflammatory cytokine release, notably IL-1β, from primed endothelial and smooth muscle cells via caspase-1-dependent mechanisms.
• oxLDL is a key driver of atherosclerosis and cardiovascular disease, making this GO term central to vascular biology research.
• Studying GO:0140052 requires integrated approaches such as RNA-seq, proteomics, and CRISPR-based perturbation of candidate genes.
• EDITGENE provides CRISPR knockout, point mutation, knock-in, overexpression, and library screening services to dissect this pathway.
Description
The Gene Ontology term GO:0140052, cellular response to oxidised low-density lipoprotein particle stimulus, defines the set of cellular processes triggered when a cell encounters oxidised low-density lipoprotein (oxLDL) particles. oxLDL is a modified form of LDL that arises from oxidative modification of lipids and apolipoproteins, and it is a major pathogenic factor in atherosclerosis and related cardiovascular diseases. Unlike native LDL, oxLDL is recognized by scavenger receptors and elicits a broad range of cellular responses, including changes in gene expression, cytokine secretion, and inflammatory signaling. Understanding this response at the molecular level is essential for identifying therapeutic targets and biomarkers in vascular disease.
cellular response to oxidised low-density lipoprotein particle stimulus At A Glance
| GO ID | GO:0140052 |
|---|---|
| GO term | cellular response to oxidised low-density lipoprotein particle stimulus |
| Ontology | biological_process |
| Synonym | cellular response to oxidised LDL particle stimulus; cellular response to oxidized LDL particle stimulus; cellular response to oxidized low-density lipoprotein particle stimulus; cellular response to ox-LDL particle stimulus; cellular response to oxLDL particle stimulus |
| Major function | Cellular sensing and response to oxidised LDL particles, including gene expression changes, cytokine secretion, and inflammatory signaling |
| Cellular context | Vascular smooth muscle cells, endothelial cells, macrophages, and other cell types exposed to oxLDL |
| Key mediators | IL-1β, caspase-1, and numerous oxLDL-responsive genes identified by transcriptomics |
| Disease relevance | Atherosclerosis, cardiovascular disease, and inflammatory disorders |
What Is GO:0140052?
According to the Gene Ontology, GO:0140052 refers to any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an oxidized lipoprotein particle stimulus. In simpler terms, it is the collection of cellular reactions—such as turning genes on or off, releasing signaling molecules, or altering cell behavior—that occur when a cell detects oxidised LDL particles in its environment.
Why Is cellular response to oxidised low-density lipoprotein particle stimulus Important in Cell Biology?
GO:0140052 is important because oxLDL is a central driver of atherosclerosis, and the cellular response to oxLDL determines plaque formation, inflammation, and disease progression. Researchers studying vascular biology, immunology, and cardiology need to understand this process to develop therapies that target oxLDL-induced inflammation and gene expression changes.
• oxLDL is a major risk factor for atherosclerosis and cardiovascular disease.
• The response involves rapid transcriptomic changes in vascular smooth muscle cells.
• oxLDL induces release of IL-1β, a key inflammatory cytokine, from primed endothelial and smooth muscle cells.
• Caspase-1-dependent mechanisms are involved in oxLDL-induced IL-1β release.
• Understanding this response can reveal therapeutic targets for cardiovascular disease.
• It links lipid metabolism, inflammation, and gene regulation.
• It is relevant to macrophage foam cell formation and plaque instability.
• It provides a model for studying cellular responses to modified lipoproteins.
• It helps explain how environmental stimuli alter cell state and activity.
• It is a focus for CRISPR-based functional genomics in vascular cells.
What Happens During cellular response to oxidised low-density lipoprotein particle stimulus?
Recognition and Early Signaling
In simple terms: The cell detects oxLDL particles and starts sending signals inside.
When oxLDL particles contact a cell, they are recognized by scavenger receptors and other surface molecules, triggering intracellular signaling cascades. This recognition leads to rapid changes in gene expression, as shown by early transcriptomic responses in human vascular smooth muscle cells exposed to oxLDL.
Transcriptional Reprogramming
In simple terms: The cell turns many genes on or off in response to oxLDL.
oxLDL induces widespread changes in the transcriptome, with hundreds of genes differentially expressed within hours. These changes affect processes such as inflammation, cell proliferation, and lipid metabolism, and are distinct from responses to native LDL.
Inflammatory Cytokine Release
In simple terms: The cell releases inflammatory molecules like IL-1β.
In primed endothelial and smooth muscle cells, oxLDL stimulates the release of IL-1β through caspase-1-dependent mechanisms. This cytokine release is a key component of the cellular response and contributes to vascular inflammation.
Caspase-1 Activation
In simple terms: A specific enzyme called caspase-1 is activated to process inflammatory signals.
oxLDL-induced IL-1β release from endothelial and smooth muscle cells occurs via different caspase-1-dependent mechanisms, highlighting cell-type-specific pathways. Caspase-1 activation is a critical step in the inflammatory response to oxLDL.
Key Genes Involved in GO:0140052 cellular response to oxidised low-density lipoprotein particle stimulus
The following genes and proteins are involved in the cellular response to oxidised low-density lipoprotein particle stimulus, based on transcriptomic and functional studies.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL1B | Encodes IL-1β, a pro-inflammatory cytokine released in response to oxLDL | Target for anti-inflammatory therapy in atherosclerosis |
| CASP1 | Encodes caspase-1, which processes IL-1β and mediates its release | Key node in oxLDL-induced inflammation |
| IL6 | Pro-inflammatory cytokine often induced by oxLDL | Marker of vascular inflammation |
| CXCL8 | Chemokine involved in neutrophil recruitment, induced by oxLDL | Potential therapeutic target |
| CCL2 | Chemokine that recruits monocytes, upregulated by oxLDL | Linked to plaque formation |
| NFKB1 | Transcription factor regulating inflammatory genes in response to oxLDL | Central regulator of oxLDL signaling |
| RELA | NF-κB subunit, activated by oxLDL | Target for modulating inflammatory response |
| MAPK1 | Kinase involved in signaling cascades triggered by oxLDL | Potential drug target |
| MAPK3 | Kinase in MAPK pathway, activated by oxLDL | Involved in gene regulation |
| JUN | Transcription factor activated by oxLDL | Regulates AP-1 target genes |
| FOS | Transcription factor component of AP-1, induced by oxLDL | Early response gene |
| ATF3 | Stress-responsive transcription factor induced by oxLDL | Modulates inflammatory signaling |
| HMOX1 | Heme oxygenase-1, antioxidant enzyme induced by oxLDL | Protective role in oxidative stress |
| SQSTM1 | Autophagy receptor, regulated by oxLDL | Links oxLDL to autophagy |
| NLRP3 | Inflammasome component involved in IL-1β maturation | Target for anti-inflammatory drugs |
| TNF | Pro-inflammatory cytokine induced by oxLDL | Contributes to vascular inflammation |
| VCAM1 | Adhesion molecule upregulated by oxLDL | Mediates leukocyte adhesion |
How Is cellular response to oxidised low-density lipoprotein particle stimulus Regulated?
The cellular response to oxidised low-density lipoprotein particle stimulus is regulated at multiple levels, including transcriptional activation of inflammatory genes and post-translational processing of cytokines. Key regulatory nodes include NF-κB and MAPK pathways, which are activated upon oxLDL exposure and drive downstream gene expression. In addition, caspase-1-dependent inflammasome activation regulates the release of IL-1β, providing a post-transcriptional control point.
cellular response to oxidised low-density lipoprotein particle stimulus and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL1B | Atherosclerosis, inflammation | Knockout in endothelial cells to assess IL-1β release |
| CASP1 | Vascular inflammation | Point mutation to abrogate caspase-1 activity |
| NFKB1 | Atherosclerosis, inflammatory signaling | Knockout in smooth muscle cells to study gene expression |
| HMOX1 | Oxidative stress, cardiovascular disease | Overexpression to test protective effects |
| NLRP3 | Inflammasome-related disorders | Knock-in of disease-associated variants |
Atherosclerosis and Cardiovascular Disease
oxLDL is a major pathogenic factor in atherosclerosis, and the cellular response to oxLDL contributes to plaque formation, inflammation, and disease progression. The release of IL-1β from endothelial and smooth muscle cells further amplifies vascular inflammation.
Inflammatory Disorders
Dysregulated cellular responses to oxLDL can lead to chronic inflammation, which is implicated in various inflammatory disorders beyond cardiovascular disease. Targeting components of this response, such as caspase-1 or IL-1β, may have therapeutic potential.
Metabolic Syndrome and Diabetes
oxLDL levels are often elevated in metabolic syndrome and diabetes, and the cellular response to oxLDL may contribute to vascular complications in these conditions.
From cellular response to oxidised low-density lipoprotein particle stimulus-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X mediate oxLDL-induced IL-1β release? | CRISPR knockout of gene X in primed endothelial cells |
| Does a specific point mutation in CASP1 alter its activity? | Point mutation knock-in in smooth muscle cells |
| Can overexpression of HMOX1 protect against oxLDL? | Overexpression of HMOX1 in vascular cells |
| What is the role of NFKB1 in oxLDL-induced transcriptome changes? | Knockout of NFKB1 followed by RNA-seq |
| Does a tagged version of IL1B affect its secretion? | Tagged knock-in of IL1B |
| Which genes are essential for oxLDL response? | Genome-wide CRISPR library screening |
How to Study the cellular response to oxidised low-density lipoprotein particle stimulus Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify oxLDL-responsive genes |
| Proteomics | Protein abundance and modifications | Quantify inflammatory proteins |
| ELISA | Cytokine secretion (e.g., IL-1β) | Measure inflammatory response |
| CRISPR knockout screening | Gene essentiality for oxLDL response | Discover novel regulators |
| Flow cytometry | Cell surface markers and viability | Assess oxLDL uptake and cell state |
| Western blot | Protein expression and cleavage | Detect caspase-1 activation |
| Immunofluorescence | Protein localization | Visualize NF-κB translocation |
Transcriptomics (RNA-seq)
RNA-seq is used to measure global changes in gene expression in response to oxLDL, as demonstrated in human vascular smooth muscle cells. This method identifies differentially expressed genes and pathways activated by oxLDL.
Proteomics and Cytokine Profiling
Proteomic approaches and cytokine assays can quantify the release of inflammatory mediators such as IL-1β from cells exposed to oxLDL. These methods help link gene expression changes to functional outcomes.
CRISPR Screening
Genome-wide CRISPR knockout screens can identify genes required for the cellular response to oxLDL, including those involved in IL-1β release and inflammatory signaling.
Imaging and Flow Cytometry
Imaging and flow cytometry can visualize oxLDL uptake, receptor binding, and downstream cellular responses at the single-cell level.
How CRISPR Can Be Used to Study GO:0140052 cellular response to oxidised low-density lipoprotein particle stimulus
Knockout
CRISPR knockout is used to delete candidate genes such as IL1B or CASP1 to determine their requirement for oxLDL-induced responses, including cytokine release.
Point Mutation
Point mutations can be introduced into genes like CASP1 to abrogate catalytic activity or into IL1B to prevent cleavage, allowing precise structure-function studies.
Knock-in
Knock-in of tagged versions of genes (e.g., IL1B with a fluorescent tag) enables tracking of protein localization and secretion in response to oxLDL.
Overexpression
Overexpression of protective genes such as HMOX1 can be achieved via CRISPR activation or lentiviral delivery to test their ability to modulate oxLDL responses.
How EDITGENE Supports cellular response to oxidised low-density lipoprotein particle stimulus Research
Researchers studying cellular response to oxidised low-density lipoprotein particle stimulus-related genes often need to determine whether a candidate gene is causally involved in oxLDL-induced phenotypes such as cytokine release or transcriptomic changes. EDITGENE provides a comprehensive suite of CRISPR services to enable these functional studies.
Contact EDITGENE today to design your custom CRISPR model for cellular response to oxidised low-density lipoprotein particle stimulus research.
Frequently Asked Questions About cellular response to oxidised low-density lipoprotein particle stimulus
What is GO:0140052?
GO:0140052 is the Gene Ontology term for cellular response to oxidised low-density lipoprotein particle stimulus, describing how cells change their state or activity in response to oxLDL.
What genes are involved in cellular response to oxidised low-density lipoprotein particle stimulus?
Key genes include IL1B, CASP1, NFKB1, and HMOX1, among others identified by transcriptomics.
How does oxLDL trigger inflammation?
oxLDL activates signaling pathways that lead to cytokine release, including IL-1β via caspase-1-dependent mechanisms.
What cell types respond to oxLDL?
Vascular smooth muscle cells, endothelial cells, and macrophages are among the cell types that respond to oxLDL.
What diseases are associated with oxLDL response?
Atherosclerosis, cardiovascular disease, and inflammatory disorders are linked to oxLDL responses.
How can I study GO:0140052 in the lab?
Common methods include RNA-seq, proteomics, cytokine assays, and CRISPR screens.
What is the role of caspase-1 in oxLDL response?
Caspase-1 processes IL-1β and mediates its release from primed endothelial and smooth muscle cells upon oxLDL exposure.
Can CRISPR be used to study oxLDL response?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools to dissect this pathway.
What transcriptomic changes occur in response to oxLDL?
oxLDL induces rapid and widespread changes in gene expression, affecting hundreds of genes in vascular smooth muscle cells.
How does EDITGENE support oxLDL research?
EDITGENE offers custom CRISPR cell models, library screening, and bioinformatics to study the cellular response to oxLDL.
Conclusion
GO:0140052 captures a critical biological process by which cells sense and respond to oxidised LDL, a key driver of cardiovascular disease. Understanding the genes and mechanisms involved provides opportunities for therapeutic intervention. EDITGENE's CRISPR services empower researchers to functionally dissect this pathway and accelerate discovery.
References
- 1. Damián-Zamacona S et al.. 2016. Early Transcriptomic Response to LDL and oxLDL in Human Vascular Smooth Muscle Cells.. PLoS One 11(10):e0163924 PMID: 27727291
- 2. Almansouri M et al.. 2022. OxLDL induces the release of IL-1β from primed human endothelial and smooth muscle cells via different caspase -1-dependent mechanisms.. Vasc Biol 4(1):11-18 PMID: 35994001
