PECAM1 - Platelet Endothelial Cell Adhesion Molecule 1

PECAM1 - Platelet Endothelial Cell Adhesion Molecule 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">pecam1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PECAM1</td>
</tr>
<tr>
<td class="label">Official Name</td>
<td>Platelet Endothelial Cell Adhesion Molecule 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17q23</td>
</tr>
<tr>
<td class="label">Gene ID</td>
<td>5175</td>
</tr>
<tr>
<td class="label">NCBI Reference</td>
<td>NM_000442</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P16284</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000261371</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Blocking Antibodies</td>
<td>Anti-PECAM1 antibodies</td>
</tr>
<tr>
<td class="label">Peptide Inhibitors</td>
<td>ITIM mimetics</td>
</tr>
<tr>
<td class="label">Soluble PECAM1</td>
<td>Recombinant sPECAM1</td>
</tr>
<tr>
<td class="label">Gene Therapy</td>
<td>siRNA/shRNA</td>
</tr>
<tr>
<td class="label">Kinase Inhibitors</td>
<td>Src family inhibitors</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/carcinoma" style="color:#ef9a9a">Carc

...

PECAM1 - Platelet Endothelial Cell Adhesion Molecule 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">pecam1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PECAM1</td>
</tr>
<tr>
<td class="label">Official Name</td>
<td>Platelet Endothelial Cell Adhesion Molecule 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17q23</td>
</tr>
<tr>
<td class="label">Gene ID</td>
<td>5175</td>
</tr>
<tr>
<td class="label">NCBI Reference</td>
<td>NM_000442</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P16284</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000261371</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Blocking Antibodies</td>
<td>Anti-PECAM1 antibodies</td>
</tr>
<tr>
<td class="label">Peptide Inhibitors</td>
<td>ITIM mimetics</td>
</tr>
<tr>
<td class="label">Soluble PECAM1</td>
<td>Recombinant sPECAM1</td>
</tr>
<tr>
<td class="label">Gene Therapy</td>
<td>siRNA/shRNA</td>
</tr>
<tr>
<td class="label">Kinase Inhibitors</td>
<td>Src family inhibitors</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/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/coronary-artery-disease" style="color:#ef9a9a">Coronary Artery Disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">38 edges</a></td>
</tr>
</table>

Introduction

Pecam1 Platelet Endothelial 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

Platelet Endothelial Cell Adhesion Molecule 1 (PECAM1) encodes a transmembrane glycoprotein expressed on endothelial cells, platelets, and leukocytes. It plays essential roles in vascular inflammation, leukocyte transmigration, and maintaining endothelial barrier function[@newman1990]. PECAM1 is particularly concentrated at endothelial cell junctions where it contributes to the formation of the endothelial barrier[@muller1989].

Gene Information

Protein Structure

PECAM1 is a type I transmembrane glycoprotein with distinctive structural features[@stockinger1990]:

• Signal peptide (1-18 aa): Directs protein to the cell membrane
• Extracellular domain (19-574 aa): Contains 6 immunoglobulin-like (Ig) domains
• Transmembrane domain (575-599 aa): Single pass alpha-helical membrane span
• Cytoplasmic tail (600-738 aa): Contains ITIM motifs and serine/threonine-rich regions

Ig-like Domains

The six extracellular Ig-like domains (D1-D6) each contain two conserved cysteine residues forming disulfide bonds. The D1-D2 domains mediate homophilic (PECAM1-PECAM1) binding, while the cytoplasmic tail contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs)[@jackson1997].

ITIM Motifs

The cytoplasmic tail contains two ITIM sequences (positions 663-668 and 686-691) that recruit phosphatases SHP-1 and SHP-2, mediating inhibitory signaling[@krystal1998].

Molecular Function

PECAM1 mediates multiple biological functions through both homophilic and heterophilic interactions[@newman1990][@delisser1997]:

Homophilic Interactions

• Endothelial junctions: PECAM1-PECAM1 binding at cell-cell contacts[@muller1989]
• Trans-endothelial migration: Mediates leukocyte passage through endothelium[@muller2011]
• Endothelial barrier maintenance: Strengthens endothelial cell junctions[@privratsky2010]

Heterophilic Interactions

• Integrin binding: Interacts with αvβ3 and α6β1 integrins[@buckley1996]
• CD38: Mediates leukocyte activation[@deaglio2000]
• Glycosaminoglycans: Binds to heparan sulfate[@kogoshi2000]

Signaling Functions

• ITIM-mediated inhibition: Recruits SHP-1/SHP-2 phosphatases[@krystal1998]
• Integrin activation: Facilitates integrin-mediated adhesion[@bird1999]
• Mechanical signaling: Functions as mechanosensor in endothelium[@chiu2008]

Signaling and Regulation

Transcriptional Control

• [NF-κB](/entities/nf-kb): Primary transcriptional regulator of PECAM1[@mahmood1999]
• AP-1: Cooperates with NF-κB for cytokine-induced expression
• KLF2/4: Shear stress-responsive transcription factors[@dekker2006]
• ETS family: Endothelial-specific expression regulators[@botting2012]

Post-translational Modifications

• Phosphorylation: Tyrosine phosphorylation activates ITIM signaling[@zhou2007]
• Glycosylation: N-linked glycosylation affects interactions[@yanaga2002]
• Proteolytic shedding: Produces soluble PECAM1 (sPECAM1)[@goldberger1994]
• Palmitoylation: Affects membrane localization[@babendreyer2017]

Regulation by Flow

• Shear stress: PECAM1 acts as mechanosensor[@chiu2008]
• Atheroprotection: Laminar flow maintains PECAM1 expression[@chiu2004]
• Dysfunction: Disturbed flow reduces PECAM1 at junctions[@hahn2012]

Disease Associations

Alzheimer's Disease (AD)

PECAM1 plays complex roles in Alzheimer's disease pathophysiology[@kalinowska2008][@grammas2011]:

• BBB dysfunction: Elevated in AD brain microvasculature; contributes to blood-brain barrier breakdown[@zlokovic2008]
• Cerebral amyloid angiopathy (CAA): Associated with vascular amyloid deposits[@weller2009]
• Endothelial activation: Markers correlate with disease severity[@blasko2000]
• Perivascular inflammation: Facilitates perivascular immune cell infiltration[@michaud2013]
• Neurovascular coupling: Dysregulation affects blood flow regulation[@iadecola2017]

Parkinson's Disease (PD)

In Parkinson's disease, PECAM1 contributes to neuroinflammation[@chen2019][@zhang2019]:

• Substantia nigra: Increased expression in dopaminergic regions[@mcgeer1988]
• Microglial activation: Mediates communication between endothelial cells and [microglia](/entities/microglia)[@nottet1996]
• [Blood-brain barrier](/entities/blood-brain-barrier): Contributes to BBB permeability in PD[@kortekaas2005]
• Disease severity: Soluble PECAM1 levels correlate with motor symptoms[@hall2012]

Stroke and Ischemic Injury

PECAM1 is critically involved in stroke pathophysiology[@zhang1998][@wang2004]:

• Ischemic injury: Rapidly upregulated after cerebral ischemia[@zhang1997]
• Reperfusion injury: Mediates post-ischemic inflammation[@petty2009]
• Angiogenesis: Involved in post-stroke blood vessel formation[@hayashi2004]
• Therapeutic target: Blocking PECAM1 reduces infarct size[@ma1999]

Multiple Sclerosis (MS)

PECAM1 participates in MS pathogenesis[@lee1999][@engelhardt2010]:

• Immune cell trafficking: Mediates leukocyte entry into CNS[@raine1995]
• Lesion formation: Elevated in active demyelinating lesions[@cannella1998]
• BBB integrity: Maintains blood-brain barrier function[@lyck2008]
• Endothelial repair: Involved in lesion recovery[@zgraggen2000]

Vascular Dementia

PECAM1 contributes to vascular cognitive impairment[@toledo2013][@iadecola2013]:

• Endothelial dysfunction: Marker of cerebrovascular pathology[@gorelick2010]
• Cerebral hypoperfusion: Contributes to reduced cerebral blood flow[@obrien2014]
• White matter lesions: Associated with small vessel disease[@wardlaw2013]
• Mixed pathology: Common comorbidity with AD[@schneider2014]

COVID-19 and Neurological Complications

Emerging evidence links PECAM1 to COVID-19-related neurological issues[@iadecola2021]:

• Endothelial infection: SARS-CoV-2 can infect endothelial cells[@varga2020]
• BBB dysfunction: COVID-associated coagulopathy affects PECAM1[@ref2021]
• Neuroinflammation: Contributes to long COVID symptoms[@paterson2021]

Expression Pattern

Basal Expression

• Endothelial cells: High expression, especially at intercellular junctions[@muller1989]
• Platelets: Abundant on platelet surface[@newman1989]
• Leukocytes: Variable; highest on monocytes, neutrophils[@demeure2000]
• Stem cells: Expressed on hematopoietic stem cells[@baumann1999]

Induced/Modulated Expression

• Cytokines: TNF-α, IL-1β upregulate expression[@mahmood1999]
• Shear stress: Laminar flow maintains; disturbed flow reduces[@dekker2006]
• Hypoxia: Induces PECAM1 expression[@chiu2005]
• Oxidized LDL: Upregulates in atherosclerotic vessels[@khan1995]

Brain Regional Distribution

• Cerebral [cortex](/brain-regions/cortex): High junctional expression on cortical vessels
• [Hippocampus](/brain-regions/hippocampus): Elevated in AD-susceptible regions[@kalinowska2008]
• Basal ganglia: High expression in PD-relevant regions[@mcgeer1988]
• White matter: Associated with active lesions in MS[@cannella1998]

Therapeutic Targeting

Clinical Considerations

• Bleeding risk: PECAM1 affects platelet function[@pdt2013]
• Therapeutic window: Timing critical for stroke treatment
• Compensatory mechanisms: Redundancy with other adhesion molecules

Clinical Significance

Diagnostic Biomarkers

• Soluble PECAM1 (sPECAM1): Elevated in various neurological conditions[@ridker1998]
• Platelet activation: PECAM1 shedding indicates platelet activation[@michelson1996]
• Endothelial injury: Marker of vascular damage[@blann2003]
• Disease monitoring: Levels track with disease progression[@hall2012]

Prognostic Applications

• Stroke outcome: Higher post-stroke PECAM1 predicts worse outcome[@castellanos2002]
• AD progression: Correlates with cognitive decline rate[@blasko2000]
• MS disability: Predicts disease severity[@orejaguevara2012]

Research Applications

• Endothelial signaling: Model system for ITIM signaling[@carman2007]
• Leukocyte trafficking: Key molecule for diapedesis studies[@muller2011]
• Mechanotransduction: Model for shear stress sensing[@chiu2008]

See Also

Related Genes and Proteins

• [ICAM1 Gene](/proteins/icam1-protein) - Intercellular Adhesion Molecule 1
• [VCAM1 Gene](/proteins/vcam1-protein) - Vascular Cell Adhesion Molecule 1
• [SELE Gene](/proteins/sele-protein) - E-selectin
• [SELP Gene](/proteins/selp-protein) - P-selectin
• [CD38 Gene](/proteins/cd38-protein) - CD38 Molecule
• [ITGAV Gene](/proteins/itgav-protein) - Integrin Alpha V (αV)
• [ITGB3 Gene](/proteins/itgb3-protein) - Integrin Beta 3 (β3)

Related Pathways

• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
• [Blood-Brain Barrier Dysfunction](/mechanisms/blood-brain-barrier-dysfunction)
• [Leukocyte Extravasation Signaling](/mechanisms/leukocyte-extravasation)
• [Coagulation Cascade](/mechanisms/coagulation-cascade)

Related Diseases

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

Background

The study of Pecam1 Platelet Endothelial 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 pecam1 discovered through SciDEX knowledge graph analysis:

Pathway Diagram

The following diagram shows the key molecular relationships involving PECAM1 - Platelet Endothelial Cell Adhesion Molecule 1 discovered through SciDEX knowledge graph analysis: