A cystine-knot miniprotein from tomato fruit inhibits endothelial cell migration and angiogenesis by affecting vascular endothelial growth factor receptor (VEGFR) activation and nitric oxide production

2015 ◽  
Vol 59 (11) ◽  
pp. 2255-2266 ◽  
Author(s):  
Davide Treggiari ◽  
Gianni Zoccatelli ◽  
Barbara Molesini ◽  
Maurizio Degan ◽  
Giuseppe Leonardo Rotino ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Tomato Fruit ◽  
Growth Factor Receptor ◽  
Endothelial Cell Migration ◽  
Nitric Oxide Production ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Measurement of free and complexed soluble vascular endothelial growth factor receptor, Flt-1, in fluid samples: development and application of two new immunoassays

2001 ◽  
Vol 100 (5) ◽  
pp. 567-575 ◽  
Author(s):  
Funmi M. BELGORE ◽  
Andrew D. BLANN ◽  
Gregory Y. LIP
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Plasma Levels ◽  
Biological Significance ◽  
Growth Factor Receptor ◽  
Soluble Form ◽  
Vascular Endothelial ◽  
Significant Difference ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. VEGF interacts with the endothelium via two membrane-spanning receptors, fms-like tyrosine kinase (Flt)-1 and kinase domain receptor. A soluble form of Flt-1 (sFlt-1) was isolated from endothelial cell media; however, its biological significance is still unknown, with limited data on plasma sFlt-1 levels in disease states. We have developed two new ELISAs for detecting free and VEGF-complexed sFlt-1, which were tested in accordance with standard validation and assessment methodologies employed in commercial settings. The intra-and inter-assay coefficients of variation are < 5% and 10% respectively, and results are highly reproducible. Applying these ELISAs in a clinical setting, we measured levels of VEGF, free and complexed sFlt-1 in citrated plasma from 40 patients with cardiovascular disease and 40 healthy controls. Median (interquartile range) plasma levels of VEGF in patients were significantly greater than controls [403 pg/ml (158–925 pg/ml) versus 113 pg/ml (33–231 pg/ml), P ⩽ 0.05]. Free sFlt-1 was significantly lower in patients compared with controls [8 ng/ml (2–22 ng/ml) versus 21 ng/ml (10–73 ng/ml), P ⩽ 0.05]. There was no significant difference in the levels of complexed sFlt-1 between the two groups. Plasma levels of VEGF-complexed sFlt-1 are minimal, despite the presence of excess free sFlt-1. Thus unbound plasma VEGF detected by ELISA may represent the majority of circulating VEGF, and justifies the measurement of plasma VEGF as an indicator of circulating VEGF levels. Furthermore, these results suggest that circulating sFlt-1 may serve as a selective inhibitor of VEGF activity, and that this regulatory mechanism may be altered by pathological conditions.

Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity

Blood ◽  
2005 ◽  
Vol 106 (7) ◽  
pp. 2347-2355 ◽  
Author(s):  
Elzafir Elsheikh ◽  
Mehmet Uzunel ◽  
Zhong He ◽  
Jan Holgersson ◽  
Grzegorz Nowak ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Functional Capacity ◽  
Peripheral Blood ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Endothelial Growth Factor

Abstract The monocyte population in blood is considered a possible source of endothelial precursors. Because endothelial-specific receptor tyrosine kinases act as regulators of endothelial cell function, we investigated whether expression of the vascular endothelial growth factor receptor-2 (VEGFR-2) on monocytes is important for their endothelial-like functional capacity. Peripheral-blood monocytes expressing vascular endothelial growth factor receptor-2 (VEGFR-2), or CD14+/VEGFR-2+, were isolated, and their phenotypic, morphologic, and functional capacities were compared with those of monocytes negative for this marker (CD14+/VEGFR-2-). CD14+/VEGFR-2+ cells constituted approximately 2% ± 0.5% of the total population of monocytes and 0.08% ± 0.04% of mononuclear cells in blood. CD14+/VEGFR-2+ cells exhibited the potential to differentiate in vitro into cells with endothelial characteristics. The cells were efficiently transduced by a lentiviral vector driving expression of the green fluorescence protein (GFP). Transplantation of GFP-transduced cells into balloon-injured femoral arteries of nude mice significantly contributed to efficient reendothelialization. CD14+/VEGFR-2- did not exhibit any of these characteristics. These data demonstrate that the expression of VEGFR-2 on peripheral blood monocytes is essential for their endothelial-like functional capacity and support the notion of a common precursor for monocytic and endothelial cell lineage. Our results help clarify which subpopulations may restore damaged endothelium and may participate in the maintenance of vascular homeostasis.

scholarly journals Redox Regulation of SERCA2 Is Required for Vascular Endothelial Growth Factor-Induced Signaling and Endothelial Cell Migration

2012 ◽  
Vol 17 (8) ◽  
pp. 1099-1108 ◽  
Author(s):  
Alicia M. Evangelista ◽  
Melissa D. Thompson ◽  
Robert M. Weisbrod ◽  
David R. Pimental ◽  
XiaoYong Tong ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Redox Regulation ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor
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