Mast Cell-Derived Mediators of Enhanced Microvascular Permeability, Vascular Permeability Factor/ Vascular Endothelial Growth Factor, Histamine, and Serotonin, Cause Leakage of Macromolecules through a New Endothelial Cell Permeability Organelle, the Vesiculo-Vacuolar Organelle

2005 ◽  
pp. 185-204 ◽  
Author(s):  
Ann M. Dvorak
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Mast Cell ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Cell Permeability ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Endothelial Cell Permeability ◽  
Endothelial Growth Factor

Vascular Permeability Factor/Vascular Endothelial Growth Factor: A Critical Cytokine in Tumor Angiogenesis and a Potential Target for Diagnosis and Therapy

2002 ◽  
Vol 20 (21) ◽  
pp. 4368-4380 ◽  
Author(s):  
Harold F. Dvorak
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Tumor Angiogenesis ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Permeability Factor ◽  
Endothelial Growth Factor

ABSTRACT: Vascular endothelial growth factor A (VEGF-A), the founding member of the vascular permeability factor (VPF)/VEGF family of proteins, is an important angiogenic cytokine with critical roles in tumor angiogenesis. This article reviews the literature with regard to VEGF-A’s multiple functions, the mechanisms by which it induces angiogenesis, and its current and projected roles in clinical oncology. VEGF-A is a multifunctional cytokine that is widely expressed by tumor cells and that acts through receptors (VEGFR-1, VEGFR-2, and neuropilin) that are expressed on vascular endothelium and on some other cells. It increases microvascular permeability, induces endothelial cell migration and division, reprograms gene expression, promotes endothelial cell survival, prevents senescence, and induces angiogenesis. Recently, VEGF-A has also been shown to induce lymphangiogenesis. Measurements of circulating levels of VEGF-A may have value in estimating prognosis, and VEGF-A and its receptors are potential targets for therapy. Recognized as the single most important angiogenic cytokine, VEGF-A has a central role in tumor biology and will likely have an important role in future approaches designed to evaluate patient prognosis. It may also become an important target for cancer therapy.

scholarly journals Vascular Permeability Factor/Vascular Endothelial Growth Factor Induces Lymphangiogenesis as well as Angiogenesis

2002 ◽  
Vol 196 (11) ◽  
pp. 1497-1506 ◽  
Author(s):  
Janice A. Nagy ◽  
Eliza Vasile ◽  
Dian Feng ◽  
Christian Sundberg ◽  
Lawrence F. Brown ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Blood Vessels ◽  
Vascular Permeability ◽  
Malignant Tumors ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Immunodeficient Mice ◽  
Permeability Factor ◽  
Endothelial Growth Factor

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A164, we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A–expressing tumors. We now report that, in addition to inducing angiogenesis, VEGF-A164 also induces a strong lymphangiogenic response. This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D. The new “giant” lymphatics generated by VEGF-A164 were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas/lymphatic malformations, perhaps implicating VEGF-A in the pathogenesis of these lesions. Whereas the angiogenic response was maintained only as long as VEGF-A was expressed, giant lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation.

scholarly journals Andes Virus Disrupts the Endothelial Cell Barrier by Induction of Vascular Endothelial Growth Factor and Downregulation of VE-Cadherin

2010 ◽  
Vol 84 (21) ◽  
pp. 11227-11234 ◽  
Author(s):  
Punya Shrivastava-Ranjan ◽  
Pierre E. Rollin ◽  
Christina F. Spiropoulou
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Virus Replication ◽  
Cell Permeability ◽  
Hantavirus Infection ◽  
Vascular Endothelial ◽  
Andes Virus ◽  
Endothelial Growth Factor

ABSTRACT Hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) are severe diseases associated with hantavirus infection. High levels of virus replication occur in microvascular endothelial cells but without a virus-induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of these diseases. VE-cadherin is a major component of adherens junctions, and its interaction with the vascular endothelial growth factor (VEGF) receptor, VEGF-R2, is important for maintaining the integrity of the endothelial barrier. Here we report that increased secreted VEGF and concomitant decreased VE-cadherin are seen at early times postinfection of human primary lung endothelial cells with an HPS-associated hantavirus, Andes virus. Furthermore, active virus replication results in increased permeability and loss of the integrity of the endothelial cell barrier. VEGF binding to VEGF-R2 is known to result in dissociation of VEGF-R2 from VE-cadherin and in VE-cadherin activation, internalization, and degradation. Consistent with this, we showed that an antibody which blocks VEGF-R2 activation resulted in inhibition of the Andes virus-induced VE-cadherin reduction. These data implicate virus induction of VEGF and reduction in VE-cadherin in the endothelial cell permeability seen in HPS and suggest potential immunotherapeutic targets for the treatment of the disease.

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