VCAM1 - Vascular Cell Adhesion Molecule 1

VCAM1 - Vascular Cell Adhesion Molecule 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">vcam1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>VCAM1</td>
</tr>
<tr>
<td class="label">Official Name</td>
<td>Vascular Cell Adhesion Molecule 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>1p21.2</td>
</tr>
<tr>
<td class="label">Gene ID</td>
<td>7412</td>
</tr>
<tr>
<td class="label">NCBI Reference</td>
<td>NM_001078</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P19320</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000162692</td>
</tr>
<tr>
<td class="label">Integrin</td>
<td>Alternative Name</td>
</tr>
<tr>
<td class="label">ITGA4/ITGB1</td>
<td>VLA-4</td>
</tr>
<tr>
<td class="label">ITGA4/ITGB7</td>
<td>α4β7</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Agent/Mechanism</td>
</tr>
<tr>
<td class="label">VLA-4 Antagonists</td>
<td>Natalizumab</td>
</tr>
<tr>
<td class="label">VLA-4 Antagonists</td>
<td>Firategrast</td>
</tr>
<tr>
<td class="label">VLA-4 Antagonists</td>
<td>Vedolizumab</td>
</tr>
<tr>
<td class="label">Blocking Antibodies</td>
<td>Anti-VCAM1 antibodies</td>
</tr>
<tr>
<td class="label">Small Molecules</td>
<td>VCAM1-VLA-4 inhibitors</td>
</tr>
<tr>
<td class="label">Gene Therapy</td>
<td>siRNA targeting VCAM1</td>

...

VCAM1 - Vascular Cell Adhesion Molecule 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">vcam1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>VCAM1</td>
</tr>
<tr>
<td class="label">Official Name</td>
<td>Vascular Cell Adhesion Molecule 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>1p21.2</td>
</tr>
<tr>
<td class="label">Gene ID</td>
<td>7412</td>
</tr>
<tr>
<td class="label">NCBI Reference</td>
<td>NM_001078</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P19320</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000162692</td>
</tr>
<tr>
<td class="label">Integrin</td>
<td>Alternative Name</td>
</tr>
<tr>
<td class="label">ITGA4/ITGB1</td>
<td>VLA-4</td>
</tr>
<tr>
<td class="label">ITGA4/ITGB7</td>
<td>α4β7</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Agent/Mechanism</td>
</tr>
<tr>
<td class="label">VLA-4 Antagonists</td>
<td>Natalizumab</td>
</tr>
<tr>
<td class="label">VLA-4 Antagonists</td>
<td>Firategrast</td>
</tr>
<tr>
<td class="label">VLA-4 Antagonists</td>
<td>Vedolizumab</td>
</tr>
<tr>
<td class="label">Blocking Antibodies</td>
<td>Anti-VCAM1 antibodies</td>
</tr>
<tr>
<td class="label">Small Molecules</td>
<td>VCAM1-VLA-4 inhibitors</td>
</tr>
<tr>
<td class="label">Gene Therapy</td>
<td>siRNA targeting VCAM1</td>
</tr>
<tr>
<td class="label">Natural Compounds</td>
<td>Curcumin, resveratrol</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">77 edges</a></td>
</tr>
</table>

Introduction

Vcam1 Vascular Cell Adhesion Molecule 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Vascular Cell Adhesion Molecule 1 (VCAM1) encodes a cell surface glycoprotein essential for leukocyte adhesion and migration across the vascular endothelium. It plays a crucial role in neuroinflammation and blood-brain barrier (BBB) dysfunction in neurodegenerative diseases[@osborn1989]. VCAM1 is expressed predominantly on endothelial cells and is dramatically upregulated at sites of inflammation[@dustin1990].

Gene Information

Protein Structure

VCAM1 is a type I transmembrane glycoprotein with distinctive structural features[@koning2009]:

• Signal peptide (1-19 aa): Directs protein to cell membrane
• Extracellular domain (20-698 aa): Contains 7 immunoglobulin-like (Ig) domains
• Transmembrane domain (699-723 aa): Single pass transmembrane helix
• Cytoplasmic tail (724-739 aa): Contains motifs for signaling and internalization

Ig-like Domains

The seven Ig-like domains (D1-D7) each contain conserved cysteine residues forming disulfide bonds. The N-terminal D1 domain contains the binding site for the integrin α4β1 (VLA-4)[@clements1994]. Alternative splicing can produce isoforms with 6 or 7 Ig domains[@cybulsky1991].

Molecular Function

VCAM1 binds primarily to the integrin α4β1 (VLA-4, ITGA4/ITGB1) and α4β7[@elices1990]:

Biological Functions

• Leukocyte adhesion: Mediates firm adhesion of circulating leukocytes to activated endothelium[@dustin1990]
• Extravasation: Facilitates transendothelial migration (diapedesis)[@muller2003]
• Cell survival: VCAM1-α4β1 interaction provides pro-survival signals[@mould2002]
• Angiogenesis: Supports new blood vessel formation[@garmysusini2005]

Signaling and Regulation

Transcriptional Control

• [NF-κB](/entities/nf-kb): Primary transcriptional activator; VCAM1 promoter contains κB sites[@collins1995]
• AP-1: Cooperates with NF-κB for cytokine-induced expression[@iademarco1992]
• GATA: Contributes to endothelial-specific expression[@minami2004]
• STAT3: Mediates cytokine-induced upregulation[@yu2005]

Inflammatory Regulation

• TNF-α: Strong inducer via NF-κB pathway[@osborn1989]
• IL-1β: Synergizes with TNF-α for maximal expression[@dustin1990]
• IFN-γ: Modulates VCAM1 expression in different cell types
• Shear stress: Mechanical forces regulate expression in blood vessels[@chiu2008]

Post-translational Modifications

• N-glycosylation: Essential for proper folding and ligand binding[@yoshida1996]
• Phosphorylation: Cytoplasmic tail phosphorylation affects signaling[@leitges2001]
• Shedding: Proteolytic cleavage produces soluble VCAM1 (sVCAM1)[@lee2006]

Disease Associations

Alzheimer's Disease (AD)

VCAM1 is critically involved in Alzheimer's disease pathophysiology[@grammas2011][@grammas2013]:

• BBB dysfunction: Elevated expression on brain endothelial cells contributes to blood-brain barrier breakdown[@zlokovic2008]
• Immune cell infiltration: Mediates peripheral immune cell (CD4+ T cells, monocytes) trafficking into the brain[@michaud2013]
• Cerebral amyloid angiopathy (CAA): Associated with amyloid deposition in cerebral vessels[@weller2009]
• Neurovascular unit: Dysregulation of VCAM1 disrupts endothelial-neuronal communication[@iadecola2017]
• Perivascular inflammation: [Pericytes](/cell-types/pericytes) and smooth muscle cells show increased VCAM1[@blair2020]

Parkinson's Disease (PD)

In Parkinson's disease, VCAM1 contributes to neuroinflammation[@zhang2019][@chen2019]:

• Substantia nigra: Increased VCAM1 expression in dopaminergic regions[@mcgeer1988]
• Microglial activation: Facilitates recruitment of peripheral macrophages[@croisier2005]
• CSF biomarkers: Elevated soluble VCAM1 in cerebrospinal fluid[@hall2012]
• Disease progression: Levels correlate with Hoehn and Yahr stage[@shi2011]
• Locus coeruleus: VCAM1 expression in noradrenergic nuclei[@gesi2001]

Multiple Sclerosis (MS)

VCAM1 is central to MS pathogenesis[@cannella1998][@engelhardt2010]:

• Immune cell trafficking: Essential for leukocyte entry into CNS[@raine1995]
• [Blood-brain barrier](/entities/blood-brain-barrier): Critical for BBB penetration by autoreactive T cells[@vajkoczy2001]
• Lesion development: High expression in active demyelinating lesions[@sobel1993]
• Therapeutic target: Natalizumab blocks VLA-4/VCAM1 interaction[@polman2006]

Stroke and Ischemic Injury

VCAM1 mediates post-ischemic inflammation[@huang2000][@wang2004]:

• Early upregulation: Rapidly induced after cerebral ischemia[@zhang1998]
• Reperfusion injury: Mediates secondary inflammatory damage[@petty2009]
• Therapeutic window: Blocking VCAM1 reduces infarct size in animal models[@vemuganti2004]
• Angiogenesis: Involved in post-stroke blood vessel repair[@hayashi2006]

Amyotrophic Lateral Sclerosis (ALS)

VCAM1 is elevated in ALS[@zhong2008]:

• Motor [cortex](/brain-regions/cortex): Increased expression in motor cortex blood vessels[@kim2016]
• Spinal cord: Mediates inflammatory cell infiltration[@rossi2012]
• Disease progression: Correlates with rate of functional decline[@fiala2010]
• Endothelial dysfunction: Part of broader neurovascular unit disruption[@miyazaki2011]

Expression Pattern

Basal Expression

• Endothelial cells: Low basal, highly inducible
• Epithelial cells: Variable expression
• Fibroblasts: Inducible by cytokines
• [Astrocytes](/entities/astrocytes): Minimal under normal conditions[@rosen1992]

Induced Expression

• Activated endothelium: Strong upregulation at sites of inflammation[@dustin1990]
• Smooth muscle cells: Inducible in pathological states[@li2010]
• Macrophages/monocytes: Express VCAM1 in inflamed tissues[@antalini1993]
• Astrocytes: Induced in reactive astrocytes (astrocytosis)[@satoh1996]

Brain Regional Specificity

• Cerebral cortex: Low baseline, induced in pathology
• [Hippocampus](/brain-regions/hippocampus): Moderate expression in AD[@grammas2011]
• Basal ganglia: High expression in PD substantia nigra[@mcgeer1988]
• White matter: Associated with MS lesions[@sobel1993]

Therapeutic Targeting

Clinical Applications

• MS treatment: Natalizumab highly effective but carries PML risk[@bloomgren2012]
• BBB modulation: VCAM1 as target for enhancing drug delivery[@nitta2003]
• Neuroprotection: Blocking VCAM1 reduces excitotoxic damage[@lawrence2003]

Clinical Significance

Diagnostic Biomarkers

• Soluble VCAM1 (sVCAM1): Elevated in AD, PD, MS, stroke[@hartung1995]
• Blood/CSF ratio: Indicates CNS vs peripheral inflammation
• Disease staging: Higher levels correlate with advanced disease[@shi2011]
• Treatment monitoring: Changes reflect therapeutic response[@trojano2003]

Prognostic Applications

• MS: Higher sVCAM1 predicts relapse risk[@rudick1999]
• Stroke: Elevated post-stroke VCAM1 predicts poor outcome[@castellanos2002]
• AD: VCAM1 levels predict rate of cognitive decline[@blasko2000]

Research Directions

• VCAM1 imaging: PET ligands for visualizing neuroinflammation[@gauberti2016]
• Single-cell analysis: VCAM1 expression in distinct immune populations[@korin2017]
• Organoid models: BBB models incorporating VCAM1 for drug testing[@brown2015]

See Also

Related Genes and Proteins

• [ICAM1 Gene](/proteins/icam1-protein) - Intercellular Adhesion Molecule 1
• [PECAM1 Gene](/proteins/pecam1-protein) - Platelet Endothelial Cell Adhesion Molecule 1
• [SELE Gene](/proteins/sele-protein) - E-selectin
• [SELP Gene](/proteins/selp-protein) - P-selectin
• [ITGA4 Gene](/proteins/itga4-protein) - Integrin Alpha 4 (α4)
• [ITGB1 Gene](/proteins/itgb1-protein) - Integrin Beta 1 (β1)
• [TNF Gene](/proteins/tnf-protein) - Tumor Necrosis Factor

Related Pathways

• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
• [Blood-Brain Barrier Dysfunction](/mechanisms/blood-brain-barrier-dysfunction)
• [TNF Signaling Pathway](/mechanisms/tnf-signaling-pathway)
• [Leukocyte Extravasation Signaling](/mechanisms/leukocyte-extravasation)

Related Diseases

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Multiple Sclerosis](/diseases/multiple-sclerosis)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
• [Vascular Dementia](/diseases/vascular-dementia)

Background

The study of Vcam1 Vascular Cell Adhesion Molecule 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

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Pathway Diagram

The following diagram shows the key molecular relationships involving vcam1 discovered through SciDEX knowledge graph analysis:

Pathway Diagram

The following diagram shows the key molecular relationships involving VCAM1 - Vascular Cell Adhesion Molecule 1 discovered through SciDEX knowledge graph analysis: