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Real-time Imaging of Endothelial Cell-cell Junctions During Neutrophil Transmigration Under Physiological Flow
Published on: August 14, 2014
Vitronectin increases vascular permeability by promoting VE-cadherin internalization at cell junctions.
Rong Li1, Meiping Ren, Ni Chen
1Drug Discovery Research Center of Luzhou Medical College, Luzhou Medical College, Luzhou, Sichuan, People's Republic of China.
Plos One
|May 19, 2012
Summary
Vitronectin (VN) regulates vascular permeability by affecting VE-cadherin. Multimeric VN, but not monomeric VN, increases VE-cadherin internalization, impacting endothelial cell function and angiogenesis.
Area of Science:
- Cell Biology
- Vascular Biology
- Extracellular Matrix
Background:
- Integrins and cadherins mediate cell-cell adhesion and signaling.
- Vitronectin (VN) is an extracellular matrix and plasma protein.
- VE-cadherin is crucial for endothelial cell (EC) adhesion and vascular integrity.
Purpose of the Study:
- To investigate if vitronectin (VN) regulates vascular permeability through VE-cadherin.
- To understand the role of VN multimerization in EC function.
Main Methods:
- Human umbilical vein EC (HUVEC) monolayers were treated with multimeric and monomeric VN.
- VE-cadherin internalization was assessed using anti-α(V)β(3) antibody, Src kinase inhibition, and knockdown.
- Vascular permeability was evaluated using a modified Miles assay and FITC-dextran leakage in a mouse hindlimb ischemia model.
Main Results:
- Multimeric VN significantly increased VE-cadherin internalization in HUVECs, an effect dependent on α(V)β(3) integrin and Src kinase.
- Monomeric VN did not induce VE-cadherin internalization.
- VN deficiency impaired vascular endothelial growth factor-induced permeability and exacerbated ischemia-induced vascular permeability and macrophage infiltration in mice.
Conclusions:
- Vitronectin plays a key role in regulating endothelial permeability via integrin-dependent effects on VE-cadherin.
- These findings highlight VN's role in endothelial function and angiogenesis in both normal and pathological states.
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