scholarly journals foxc1a and foxc1b differentially regulate angiogenesis from arteries and veins by modulating Vascular Endothelial Growth Factor signalling

2018 ◽  
Author(s):  
Zhen Jiang ◽  
Teri Evans ◽  
Aaron M. Savage ◽  
Matthew Loose ◽  
Timothy J.A. Chico ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Notch Signalling ◽  
Receptor Expression ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Vascular Networks ◽  
Growth Factor Signalling ◽  
Segmental Arteries ◽  
Endothelial Growth Factor

AbstractThe forkhead transcription factors Foxc1 and Foxc2 are essential to establish intact vascular networks in mammals. How these genes interact with endothelial signalling pathways to exert their functions remains incompletely understood. We have generated novel zebrafish mutants in foxc1a and foxc1b, the zebrafish orthologues of mammalian Foxc1, to determine their function during angiogenesis. foxc1a mutants display abnormal formation of cranial veins including the primordial hindbrain channels (PHBC), reduced Vascular Endothelial Growth Factor (VEGF) receptor expression in these and loss of central arteries. foxc1b mutants are normal, whereas foxc1a; foxc1b double mutants exhibit ectopic angiogenesis from trunk segmental arteries. Dll4/Notch signalling is reduced in foxc1a; foxc1b double mutant arteries and ectopic angiogenesis can be suppressed by induction of Notch or inhibition of Vegfc signalling. We conclude that foxc1a and foxc1b play compensatory and context-dependent roles to co-ordinate angiogenesis by promoting venous sprouting via induction of VEGF receptor expression whilst antagonising arterial sprouting by inducing Dll4/Notch signalling. foxc1a/b mediated induction of both pro- and anti-angiogenic axes of VEGF-Dll4/Notch negative feedback imparts competition to balance arterial and venous angiogenesis within developing vascular beds.Summary Statementfoxc1a and foxc1b promote angiogenesis from veins and suppress angiogenesis from arteries by promoting competing pro-angiogenic Vascular Endothelial Growth Factor signalling, and anti-angiogenic Dll4/Notch signalling in zebrafish embryos.

scholarly journals Regulation of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR by estradiol through VEGF in uterus

2006 ◽  
Vol 188 (1) ◽  
pp. 91-99 ◽  
Author(s):  
M A J Hervé ◽  
G Meduri ◽  
F G Petit ◽  
T S Domet ◽  
G Lazennec ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Receptor Expression ◽  
Maximal Response ◽  
Target Cells ◽  
Vegf Receptor ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

The induction of vascular endothelial growth factor (VEGF) expression by 17β-estradiol (E2) in many target cells, including epithelial cells, fibroblasts and smooth muscle cells, suggests a role for this hormone in the modulation of angiogenesis and vascular permeability. We have already described a cyclic increase in Flk-1/KDR-expressing capillaries in the human endometrium during the proliferative and mid-secretory phases, strongly suggestive of an E2 effect on Flk-1/KDR expression in the endometrial capillaries. However, it is unclear whether these processes are due to a direct effect of E2 on endothelial cells. Using immunohistochemistry, we report an increase in Flk-1/KDR expression in endometrial capillaries of ovariectomized mice treated with E2, or both E2 and progesterone. This process is mediated through estrogen receptor (ER) activation. In vitro experiments using quantitative RT-PCR analysis demonstrate that Flk-1/KDR expression was not regulated by E2 in human endothelial cells from the microcirculation (HMEC-1) or macrocirculation (HUVEC), even in endothelial cells overexpressing ERα or ERβ after ER-mediated adenovirus infection. In contrast, Flk-1/KDR expression was up-regulated by VEGF itself, in a time- and dose-dependent manner, with the maximal response at 10 ng/ml. Thus, we suggest that E2 up-regulates Flk-1/KDR expression in vivo in endothelial cells mainly through the modulation of VEGF by a paracrine mechanism. It is currently unknown whether or not the endothelial origin might account for differences in the E2-modulation of VEGF receptor expression, particularly in relation to the vascular bed of sex steroid-responsive tissues.

A vascular endothelial growth factor 121 (VEGF121)-based dual PET/optical probe for in vivo imaging of VEGF receptor expression

Biomaterials ◽  
2013 ◽  
Vol 34 (28) ◽  
pp. 6839-6845 ◽  
Author(s):  
Choong Mo Kang ◽  
Hyun-Jung Koo ◽  
Kyo Chul Lee ◽  
Yearn Seong Choe ◽  
Joon Young Choi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
In Vivo Imaging ◽  
Optical Probe ◽  
Receptor Expression ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in placenta of hyperglycemic pregnant women☆

Placenta ◽  
2010 ◽  
Vol 31 (9) ◽  
pp. 770-780 ◽  
Author(s):  
L. Pietro ◽  
S. Daher ◽  
M.V.C. Rudge ◽  
I.M.P. Calderon ◽  
D.C. Damasceno ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pregnant Women ◽  
Receptor Expression ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant

1999 ◽  
Vol 97 (3) ◽  
pp. 303-312 ◽  
Author(s):  
Catheryne WHITTLE ◽  
Kathleen GILLESPIE ◽  
Rebecca HARRISON ◽  
Peter W. MATHIESON ◽  
Steve J. HARPER
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Reverse Transcription ◽  
Splice Variant ◽  
Receptor Expression ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Reverse Transcription Pcr ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) mediates increased vascular permeability and endothelial mitogenesis, and may orchestrate normal glomerular permselectivity and proteinuria. Distinct isoforms result from differential gene splicing. VEGF binds to two cell surface tyrosine-kinase receptors, KDR (kinase domain region) and Flt-1 (fms-like tyrosine kinase-1). The latter also exists in a soluble form (sFlt), which is inhibitory. We have studied patterns of VEGF-isoform and VEGF-receptor expression in isolated single normal human glomeruli. mRNA from 190 glomeruli (from 20 individuals) was harvested on to magnetic beads, and nested reverse transcription–PCR was performed using primers for the VEGF isoforms and VEGF receptors. Simultaneous nested reverse transcription–PCR for CD45 was conducted in order to exclude leucocyte contamination. Unexpected products were isolated, cloned and sequenced. Multiple patterns of glomerular VEGF mRNA isoform expression were identified. Most frequently (58%), all three common forms were expressed. VEGF189 (i.e. 189-amino-acid form of VEGF) was expressed in 63%, VEGF165 in 85% and VEGF121 in 84% of glomeruli. Two unexpected PCR products were also identified: 18% of glomeruli expressed VEGF145, and 27% of glomeruli expressed a new truncated VEGF splice variant, VEGF148, lacking exon 6, the terminal part of exon 7 and exon 8. Multiple patterns of VEGF-receptor expression were also identified, the most common being expression of all three isoforms (28%). Overall, KDR was seen in 59% of glomeruli, Flt-1 in 45% and sFlt in 57%. Thus the expression of VEGF within normal glomeruli is complex and variable, with inter- and intra-individual variation. Furthermore, sFlt appears to be the co-dominant form of VEGF receptor expressed within glomeruli, suggesting that, in healthy individuals, a degree of VEGF autoregulation is the norm. The physiological importance of VEGF148 remains to be confirmed.

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