GO:1904997 regulation of leukocyte adhesion to arterial endothelial cell: Vascular Inflammation Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1904997 describes any process that modulates the frequency, rate or extent of leukocyte adhesion to arterial endothelial cells, a critical early step in atherosclerosis and arterial inflammation.
• Arterial endothelial cells are functionally distinct from venous endothelium and can be modeled using human pluripotent stem cell-derived arterial endothelial cells.
• Leukocyte adhesion to arterial endothelium is driven by adhesion molecules, chemokines, and inflammatory signaling, including Src/AKT1/NF-kB and interleukin-1 pathways.
• Mitochondrial fission and reactive oxygen species are emerging regulators of endothelial inflammation and leukocyte recruitment.
• Annexin A8 deficiency delays atherosclerosis progression, highlighting novel regulators of arterial leukocyte adhesion.
• Myeloperoxidase aggravates thoracic aortic aneurysm in Marfan disease, linking leukocyte adhesion regulators to aortic pathology.
Description
GO:1904997, regulation of leukocyte adhesion to arterial endothelial cell, is a biological process term that encompasses any mechanism controlling the frequency, rate, or extent of leukocyte binding to the arterial endothelium. This process is a hallmark of early atherogenesis and arterial inflammatory diseases, where circulating leukocytes adhere to activated arterial endothelial cells and initiate plaque formation. Understanding this regulation is essential for developing therapies targeting cardiovascular inflammation. The arterial endothelium is not a passive barrier; it actively responds to inflammatory stimuli by upregulating adhesion molecules and chemokines, thereby recruiting leukocytes. Recent studies have identified diverse molecular players, including Src/AKT1/NF-kB signaling, annexin A8, mitochondrial fission, and interleukin-1, that modulate this process. This article synthesizes current knowledge on the regulation of leukocyte adhesion to arterial endothelial cells, covering its definition, mechanisms, key genes, disease relevance, and research methodologies.
regulation of leukocyte adhesion to arterial endothelial cell At A Glance
| GO ID | GO:1904997 |
|---|---|
| GO term | regulation of leukocyte adhesion to arterial endothelial cell |
| Ontology | biological_process |
| Synonym | none |
| Major function | Modulates the frequency, rate or extent of leukocyte adhesion to arterial endothelial cells |
| Related processes | leukocyte adhesion, endothelial cell activation, inflammation |
| Disease relevance | Atherosclerosis, cardiovascular disease, aortic aneurysm |
| Research models | Human pluripotent stem cell-derived arterial endothelial cells, mouse models of atherosclerosis |
What Is GO:1904997?
According to the Gene Ontology, GO:1904997 is defined as any process that modulates the frequency, rate or extent of leukocyte adhesion to arterial endothelial cell. In other words, it includes all molecular events that either promote or inhibit the attachment of white blood cells to the lining of arteries. This regulation can occur through changes in adhesion molecule expression, chemokine signaling, or endothelial cell activation state.
Why Is regulation of leukocyte adhesion to arterial endothelial cell Important in Cell Biology?
Dysregulation of leukocyte adhesion to arterial endothelial cells is a central event in the initiation and progression of atherosclerosis, the leading cause of cardiovascular disease worldwide. This process also contributes to other arterial pathologies such as aortic aneurysm and vasculitis. Understanding its regulation provides opportunities for therapeutic intervention to reduce arterial inflammation and plaque formation.
• Leukocyte adhesion to arterial endothelium is an early step in atherosclerosis.
• Arterial endothelial cells differ from venous endothelial cells in gene expression and function.
• Inflammatory signaling pathways such as Src/AKT1/NF-kB regulate leukocyte adhesion.
• Interleukin-1 is a key cytokine in coronary artery disease and modulates endothelial adhesion.
• Mitochondrial fission promotes endothelial inflammation and leukocyte recruitment.
• Reactive oxygen species contribute to microvascular dysfunction and leukocyte adhesion.
• Annexin A8 deficiency delays atherosclerosis progression, indicating its role in leukocyte adhesion.
• Myeloperoxidase aggravates thoracic aortic aneurysm in Marfan disease, linking to leukocyte adhesion.
• Targeting leukocyte adhesion regulators may reduce cardiovascular events.
• Human pluripotent stem cell-derived arterial endothelial cells provide a platform for studying this process.
What Happens During regulation of leukocyte adhesion to arterial endothelial cell?
Endothelial Activation and Adhesion Molecule Expression
In simple terms: Arterial endothelial cells become activated by inflammatory signals and start displaying sticky proteins on their surface.
In response to inflammatory cytokines such as interleukin-1, arterial endothelial cells upregulate adhesion molecules including VCAM-1, ICAM-1, and E-selectin. This upregulation is mediated by signaling pathways such as Src/AKT1/NF-kB. The expression of these adhesion molecules is a prerequisite for leukocyte capture and rolling.
Leukocyte Capture and Rolling
In simple terms: White blood cells slow down and roll along the artery wall by interacting with sticky proteins.
Leukocytes initially tether and roll on the endothelial surface through interactions between selectins and their ligands. This rolling is a reversible step that allows leukocytes to sample the endothelial environment for chemokines. The regulation of this step involves modulation of selectin expression and function.
Chemokine-Mediated Activation and Firm Adhesion
In simple terms: Chemical signals activate the white blood cells to stick firmly to the artery wall.
Chemokines presented on the endothelial surface activate leukocyte integrins, leading to firm adhesion. This process is regulated by chemokine production and presentation by arterial endothelial cells. Interleukin-1 signaling is a key regulator of chemokine expression in coronary artery disease.
Transmigration and Plaque Formation
In simple terms: White blood cells squeeze through the artery wall and contribute to plaque buildup.
After firm adhesion, leukocytes transmigrate across the endothelium into the arterial intima, where they contribute to foam cell formation and atherosclerotic plaque development. Regulation of leukocyte adhesion directly impacts the rate of transmigration and plaque progression.
Resolution and Negative Regulation
In simple terms: The body has ways to stop white blood cells from sticking too much.
Negative regulators of leukocyte adhesion include anti-inflammatory cytokines and factors that maintain endothelial quiescence. For example, annexin A8 deficiency delays atherosclerosis progression, suggesting that annexin A8 promotes leukocyte adhesion. Understanding these negative regulators is important for therapeutic strategies.
Key Genes Involved in GO:1904997 regulation of leukocyte adhesion to arterial endothelial cell
The following genes and proteins are key players in the regulation of leukocyte adhesion to arterial endothelial cells, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SRC | Kinase in Src/AKT1/NF-kB signaling pathway | Inhibition reduces leukocyte adhesion in acute lung injury models |
| AKT1 | Serine/threonine kinase in inflammatory signaling | Part of Src/AKT1/NF-kB axis regulating adhesion |
| NFKB1 | Transcription factor controlling adhesion molecule expression | Central regulator of endothelial activation |
| ANXA8 | Annexin A8, involved in membrane dynamics | Deficiency delays atherosclerosis progression |
| IL1B | Interleukin-1 beta, pro-inflammatory cytokine | Key regulator in coronary artery disease |
| VCAM1 | Vascular cell adhesion molecule 1 | Mediates leukocyte firm adhesion to arterial endothelium |
| ICAM1 | Intercellular adhesion molecule 1 | Mediates leukocyte firm adhesion |
| SELE | E-selectin, mediates leukocyte rolling | Early adhesion molecule in arterial inflammation |
| SELL | L-selectin, leukocyte rolling | Involved in initial capture |
| ITGB2 | Integrin beta 2, firm adhesion | Leukocyte integrin for firm adhesion |
| ITGAL | Integrin alpha L, firm adhesion | Leukocyte integrin for firm adhesion |
| CCL2 | Monocyte chemoattractant protein-1 | Chemokine regulating leukocyte recruitment |
| CXCL1 | Chemokine for neutrophil recruitment | Regulates leukocyte adhesion |
| MPO | Myeloperoxidase, oxidative enzyme | Aggravates thoracic aortic aneurysm in Marfan disease |
| DNM1L | Dynamin-related protein 1, mitochondrial fission | Mediates endothelial inflammation |
| TNF | Tumor necrosis factor, pro-inflammatory cytokine | Induces adhesion molecule expression |
| NOS3 | Endothelial nitric oxide synthase | Regulates endothelial function and leukocyte adhesion |
How Is regulation of leukocyte adhesion to arterial endothelial cell Regulated?
The regulation of leukocyte adhesion to arterial endothelial cells is controlled by multiple signaling pathways. The Src/AKT1/NF-kB pathway is a key positive regulator, as inhibition of Src or AKT1 reduces NF-kB activation and adhesion molecule expression. Interleukin-1 signaling amplifies endothelial activation and chemokine production. Mitochondrial fission, mediated by DNM1L, promotes endothelial inflammation and leukocyte adhesion. Reactive oxygen species, including those from myeloperoxidase, can enhance adhesion. Conversely, annexin A8 appears to promote atherosclerosis, as its deficiency delays progression. These pathways are potential therapeutic targets.
regulation of leukocyte adhesion to arterial endothelial cell and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SRC | Acute lung injury, inflammation | Src knockout mice, LPS-induced lung injury |
| ANXA8 | Atherosclerosis | Anxa8 knockout mice, atherosclerosis-prone background |
| IL1B | Coronary artery disease | Il1b knockout mice, myocardial infarction models |
| MPO | Thoracic aortic aneurysm in Marfan disease | Mpo knockout mice, Marfan mouse model |
| DNM1L | Endothelial inflammation | Endothelial-specific Drp1 knockout mice |
Atherosclerosis and Cardiovascular Disease
Leukocyte adhesion to arterial endothelial cells is a critical early event in atherosclerosis. Endothelial activation and subsequent leukocyte recruitment lead to plaque formation and cardiovascular events. Interleukin-1, a major cytokine in coronary artery disease, regulates this process. Targeting leukocyte adhesion regulators may reduce atherosclerotic burden.
Aortic Aneurysm and Marfan Syndrome
Myeloperoxidase aggravates thoracic aortic aneurysm formation in Marfan disease, partly through promoting leukocyte adhesion and oxidative stress. This highlights the role of leukocyte-endothelial interactions in aortic wall degeneration.
Acute Lung Injury and Ischemia/Reperfusion
Norwogonin attenuates LPS-induced acute lung injury by inhibiting Src/AKT1/NF-kB signaling, which regulates leukocyte adhesion. Reactive species-induced microvascular dysfunction in ischemia/reperfusion also involves leukocyte adhesion. These conditions share mechanisms with arterial inflammation.
From regulation of leukocyte adhesion to arterial endothelial cell-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate leukocyte adhesion to arterial endothelium? | Endothelial-specific knockout of gene X in mice, intravital microscopy |
| Does a point mutation in gene X affect adhesion? | Knock-in mice with point mutation, flow chamber assays |
| Does overexpression of gene X increase adhesion? | Endothelial-specific transgenic overexpression, leukocyte adhesion assays |
| Does gene X interact with adhesion molecules? | Tagged knock-in for co-immunoprecipitation, proximity ligation |
| What is the role of gene X in atherosclerosis? | Bone marrow chimera or LDLR-/- background with gene X modification |
| Can human arterial endothelial cells model this process? | Human pluripotent stem cell-derived arterial endothelial cells |
How to Study the regulation of leukocyte adhesion to arterial endothelial cell Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Flow adhesion assay | Number of adherent leukocytes | Testing gene knockout effect on adhesion |
| Intravital microscopy | Leukocyte rolling and adhesion in vivo | Studying arterial inflammation in mice |
| RNA-seq | Gene expression changes | Identifying adhesion molecules and chemokines |
| Phosphoproteomics | Signaling pathway activation | Discovering regulators of endothelial activation |
| Immunofluorescence | Protein localization and expression | Visualizing adhesion molecules on endothelium |
| ELISA | Cytokine and chemokine levels | Measuring inflammatory mediators |
| Western blot | Protein expression and phosphorylation | Validating signaling changes |
In Vitro Adhesion Assays
Leukocyte adhesion to arterial endothelial cells can be measured using static or flow-based adhesion assays. Endothelial cells are activated with cytokines such as TNF or IL-1, and fluorescently labeled leukocytes are allowed to adhere. The number of adherent cells is quantified by microscopy or flow cytometry. This method is used to test the effect of gene knockouts or inhibitors.
Intravital Microscopy
Intravital microscopy allows real-time visualization of leukocyte-endothelial interactions in living animals. This technique can assess rolling, adhesion, and transmigration in arterial vessels. It is valuable for studying the regulation of leukocyte adhesion in vivo.
Gene Expression Analysis
RNA-seq or qPCR can measure the expression of adhesion molecules and chemokines in arterial endothelial cells. This helps determine whether a gene of interest regulates the transcriptional program of endothelial activation.
Proteomic and Phosphoproteomic Profiling
Mass spectrometry-based proteomics can identify changes in protein expression and phosphorylation in endothelial cells upon activation. This approach can reveal signaling pathways regulating leukocyte adhesion.
How CRISPR Can Be Used to Study GO:1904997 regulation of leukocyte adhesion to arterial endothelial cell
Knockout
CRISPR knockout of candidate genes in arterial endothelial cells or mouse models can determine whether the gene is required for leukocyte adhesion. For example, knockout of Src or Akt1 would test their role in the Src/AKT1/NF-kB pathway. Endothelial-specific knockout avoids systemic effects.
Point Mutation
Point mutations can be introduced to study specific phosphorylation sites or functional domains. For instance, mutating a key phosphorylation site in AKT1 could reveal its importance in regulating adhesion molecule expression. This approach provides mechanistic insights.
Knock-in
Knock-in of tagged proteins (e.g., GFP or HA) allows visualization and immunoprecipitation of endogenous proteins. Tagging ANXA8 could help track its localization during atherosclerosis. Knock-in of reporter genes can also monitor promoter activity.
Overexpression
Overexpression of a gene of interest in endothelial cells can test whether it is sufficient to induce leukocyte adhesion. For example, overexpressing IL1B might enhance adhesion. This is useful for gain-of-function studies.
How EDITGENE Supports regulation of leukocyte adhesion to arterial endothelial cell Research
Researchers studying regulation of leukocyte adhesion to arterial endothelial cell-related genes often need to determine whether a candidate gene is causally involved in this process. EDITGENE provides comprehensive CRISPR gene editing services to create precisely modified cell models and animal models, enabling functional validation of genes identified in genomic or proteomic screens.
Contact EDITGENE today to design your custom CRISPR model for regulation of leukocyte adhesion to arterial endothelial cell research.
Frequently Asked Questions About regulation of leukocyte adhesion to arterial endothelial cell
What is GO:1904997?
GO:1904997 is a Gene Ontology term for the biological process 'regulation of leukocyte adhesion to arterial endothelial cell', defined as any process that modulates the frequency, rate or extent of leukocyte adhesion to arterial endothelial cell.
What genes are involved in regulation of leukocyte adhesion to arterial endothelial cell?
Key genes include SRC, AKT1, NFKB1, ANXA8, IL1B, VCAM1, ICAM1, SELE, and MPO, among others, as identified in published studies.
Why is leukocyte adhesion to arterial endothelium important?
It is an early step in atherosclerosis and arterial inflammation, contributing to cardiovascular disease.
How is leukocyte adhesion to arterial endothelial cells studied?
Common methods include flow adhesion assays, intravital microscopy, RNA-seq, and proteomics.
What diseases are associated with dysregulated leukocyte adhesion to arterial endothelium?
Atherosclerosis, coronary artery disease, aortic aneurysm, and acute lung injury are associated.
What is the role of interleukin-1 in this process?
Interleukin-1 is a pro-inflammatory cytokine that promotes endothelial activation and leukocyte adhesion, and is implicated in coronary artery disease.
How does mitochondrial fission affect leukocyte adhesion?
Mitochondrial fission mediates endothelial inflammation and can enhance leukocyte adhesion.
What is the role of annexin A8 in atherosclerosis?
Annexin A8 deficiency delays atherosclerosis progression, suggesting it promotes leukocyte adhesion and plaque formation.
Can human pluripotent stem cell-derived arterial endothelial cells be used to study this process?
Yes, these cells provide a relevant human model for studying arterial endothelial function and leukocyte adhesion.
What CRISPR models are available to study this process?
Knockout, point mutation, knock-in, and overexpression models can be generated in endothelial cells or mice to study gene function in leukocyte adhesion.
Conclusion
The regulation of leukocyte adhesion to arterial endothelial cells (GO:1904997) is a critical biological process in vascular inflammation and atherosclerosis. Key signaling pathways and genes, including Src/AKT1/NF-kB, interleukin-1, annexin A8, and mitochondrial fission, have been identified as regulators. Understanding these mechanisms offers opportunities for therapeutic intervention. Advanced CRISPR models and screening technologies, such as those provided by EDITGENE, will continue to accelerate discoveries in this field.
References
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- 2. Gutiérrez-Muñoz C et al.. 2025. Annexin A8 deficiency delays atherosclerosis progression.. Clin Transl Med 15(1):e70176 PMID: 39835780
- 3. Badimon L et al.. 1992. Endothelium and atherosclerosis.. J Hypertens Suppl 10(2):S43-50 PMID: 1593302
- 4. Yu H et al.. 2019. Reactive species-induced microvascular dysfunction in ischemia/reperfusion.. Free Radic Biol Med 135:182-197 PMID: 30849489
- 5. Zhang J et al.. 2017. Functional characterization of human pluripotent stem cell-derived arterial endothelial cells.. Proc Natl Acad Sci U S A 114(30):E6072-E6078 PMID: 28696312
- 6. Forrester SJ et al.. 2020. Mitochondrial Fission Mediates Endothelial Inflammation.. Hypertension 76(1):267-276 PMID: 32389075
- 7. Oikonomou E et al.. 2022. Interleukin-1 in Coronary Artery Disease.. Curr Top Med Chem 22(28):2368-2389 PMID: 36263481
- 8. Mehrkens D et al.. 2026. Myeloperoxidase aggravates thoracic aortic aneurysm formation in Marfan disease.. Cardiovasc Res 122(2):230-244 PMID: 41403006
