scholarly journals Evaluate the response of Apoptosis, Angiogenesis and Cancer Therapies

2018 ◽  
Vol 2 (1) ◽  
pp. 01-08
Author(s):  
Chathura Gayan
Keyword(s):  
Fas Ligand ◽  
Vascular Endothelial Cells ◽  
Pigment Epithelium ◽  
Angiogenesis Inhibitors ◽  
Cancer Therapies ◽  
Vascular Endothelial ◽  
Pigment Epithelium Derived Factor ◽  
Distinct Cell ◽  
Traditional Therapies ◽  
Endothelial Growth Factor

Angiogenesis, the growth of new blood vessels from the existing vasculature, and is maintained in adult tissues by the balanced presence of both angiogenic inducers and inhibitors in the tissue milieu. When inducers predominate, vascular endothelial cells (VECs) become activated and in this activated VECs, distinct cell signaling pathways are initiated providing the specificity of anti-angiogenic therapies to the tumor vasculature. VEC apoptosis has been well documented in regressing vessels, and it has been shown that, in addition to activating the VECs, some inducers such as vascular endothelial growth factor also up-regulate Fas expression, thus sensitizing the cell to apoptotic stimuli. Endogenous angiogenesis inhibitors, such as thrombospondin-1(TSP-1) and pigment epithelium-derived factor (PEDF), stimulate signaling cascades within the VECs and also induce the expression of Fas ligand in activated VECs. Therefore, when inhibitors predominate, the apoptotic cascade is initiated ,thus anti-angiogenic therapies can target the inducer supply or directly target the VECs. Although clinical studies suggest that anti-angiogenic therapies may prove to be most effective when used in combination with traditional therapies

scholarly journals PEDF expression regulates the proangiogenic and proinflammatory phenotype of the lung endothelium

2014 ◽  
Vol 306 (7) ◽  
pp. L620-L634 ◽  
Author(s):  
Eui Seok Shin ◽  
Christine M. Sorenson ◽  
Nader Sheibani
Keyword(s):  
Pigment Epithelium ◽  
Cell Types ◽  
Vascular Endothelial ◽  
Multifunctional Protein ◽  
Vascular Walls ◽  
Pigment Epithelium Derived Factor ◽  
Lung Endothelium ◽  
Oxide Synthase ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Growth Factor

Pigment epithelium-derived factor (PEDF) is a multifunctional protein with important roles in regulation of inflammation and angiogenesis. It is produced by various cell types, including endothelial cells (EC). However, the cell autonomous impact of PEDF on EC function needs further investigation. Lung EC prepared from PEDF-deficient (PEDF−/−) mice were more migratory and failed to undergo capillary morphogenesis in Matrigel compared with wild type (PEDF+/+) EC. Although no significant differences were observed in the rates of apoptosis in PEDF−/− EC compared with PEDF+/+ cells under basal or stress conditions, PEDF−/− EC proliferated at a slower rate. PEDF−/− EC also expressed increased levels of proinflammatory markers, including vascular endothelial growth factor, inducible nitric oxide synthase, vascular cell adhesion molecule-1, as well as altered cellular junctional organization, and nuclear localization of β-catenin. The PEDF−/− EC were also more adhesive, expressed decreased levels of thrombospondin-2, tenascin-C, and osteopontin, and increased fibronectin. Furthermore, we showed lungs from PEDF−/− mice exhibited increased expression of macrophage marker F4/80, along with increased thickness of the vascular walls, consistent with a proinflammatory phenotype. Together, our data suggest that the PEDF expression makes significant contribution to modulation of the inflammatory and angiogenic phenotype of the lung endothelium.

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