Interendothelial junctions and their role in the control of angiogenesis, vascular permeability and leukocyte

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E Dejana1, R Spagnuolo, G Bazzoni

  • 1Istituto di Ricerche Farmacologiche Mario Negri, Italy. dejana@marionegri.it

Thrombosis and Haemostasis
|August 7, 2001
PubMed

Insights

Vascular endothelial (VE)-cadherin and junctional adhesion molecule 1 (JAM-1) are key proteins in endothelial cell junctions. Their functions in vascular hemostasis, angiogenesis, and leukocyte infiltration are crucial for vascular health.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Vascular Biology

Background:

  • Endothelial cell-cell junctions are critical for vascular hemostasis.
  • VE-cadherin and JAM-1 are junctional proteins located at adherens and tight junctions, respectively.

Purpose of the Study:

  • To explore the roles of VE-cadherin and JAM-1 in endothelial cell function.
  • To investigate VE-cadherin's potential as a target for anti-angiogenic therapy.
  • To understand JAM-1's molecular interactions and functions in regulating vascular permeability and leukocyte transmigration.

Main Methods:

  • Analysis of VE-cadherin expression and function in endothelial cells.
  • Investigation of VE-cadherin's role in vascular structure organization.
  • Study of the effects of permeability-increasing agents and leukocytes on VE-cadherin/catenin organization.
  • Characterization of JAM-1's extracellular and intracellular domains, including its homophilic binding and PDZ-binding motif interactions.
  • Exploration of JAM-1's involvement in paracellular permeability and leukocyte transmigration.

Main Results:

  • VE-cadherin is specifically expressed in endothelial cells and is essential for normal vascular structure formation.
  • VE-cadherin's adhesive activity is a potential target for anti-angiogenic therapies.
  • VE-cadherin organization is modulated by permeability factors and leukocytes, suggesting a role in vascular permeability and infiltration.
  • JAM-1, an integral membrane protein, exhibits homophilic dimerization and interacts with intracellular proteins via its PDZ-binding motif.
  • JAM-1's molecular interactions are linked to its functions in controlling paracellular permeability and leukocyte transmigration.

Conclusions:

  • VE-cadherin is a critical regulator of endothelial cell junctions, vascular integrity, and angiogenesis, presenting a target for anti-angiogenic strategies.
  • JAM-1 plays a significant role in regulating endothelial barrier function and leukocyte trafficking through its molecular interactions.

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