INT204721

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Context Info
Confidence 0.73
First Reported 2007
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 30
Total Number 30
Disease Relevance 4.64
Pain Relevance 0.15

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cell differentiation (FLT1) endosome (FLT1) Golgi apparatus (FLT1)
cytoplasm (FLT1) extracellular space (FLT1) extracellular region (FLT1)
Anatomy Link Frequency
plasma 6
endothelial cells 4
section 3 1
platelet 1
endothelium 1
FLT1 (Homo sapiens)
Pain Link Frequency Relevance Heat
ischemia 52 68.56 Quite High
tolerance 24 59.44 Quite High
cytokine 27 55.36 Quite High
addiction 72 46.72 Quite Low
Inflammation 30 30.28 Quite Low
positron emission tomography 25 25.44 Quite Low
pain flank 1 13.84 Low Low
antagonist 73 5.00 Very Low Very Low Very Low
metalloproteinase 72 5.00 Very Low Very Low Very Low
Central nervous system 24 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Hypoxia 25 99.82 Very High Very High Very High
Fibromyalgia 29 96.92 Very High Very High Very High
Cancer 228 94.72 High High
Pre-eclampsia 239 92.96 High High
Peritonitis 3 90.00 High High
Coronary Artery Disease 146 87.12 High High
Disease Progression 4 86.96 High High
Peripheral Arterial Disease 433 85.76 High High
Renal Cancer 15 85.32 High High
Proteinuria 10 82.68 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The Flt-1 gene is located in the chromosome region 13q12 and consists of 30 exons and 29 introns [11,12].
Localization (located) of Flt-1 gene
1) Confidence 0.73 Published 2008 Journal BMC Med Genet Section Body Doc Link PMC2496902 Disease Relevance 0.06 Pain Relevance 0
Among the major endothelial cell surface receptor targets for these VEGF isoforms are: the tyrosine kinases VEGFR1 (Flt-1; UniProt accession P17948-1) and VEGFR2 (mouse Flk-1; human KDR; UniProt accession P35968); as well as the co-receptor neuropilin-1 (NRP1; UniProt accession O14786), which couples directly with VEGFR1, and indirectly with VEGFR2 through non-overlapping binding sites on VEGF165 [7].


Localization (targets) of VEGFR1 in endothelial cell
2) Confidence 0.71 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0.46 Pain Relevance 0.03
Sensitivity to VEGF-binding affinity of VEGFR1 and VEGFR2
Localization (affinity) of VEGFR1
3) Confidence 0.71 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Among the major endothelial cell surface receptor targets for these VEGF isoforms are: the tyrosine kinases VEGFR1 (Flt-1; UniProt accession P17948-1) and VEGFR2 (mouse Flk-1; human KDR; UniProt accession P35968); as well as the co-receptor neuropilin-1 (NRP1; UniProt accession O14786), which couples directly with VEGFR1, and indirectly with VEGFR2 through non-overlapping binding sites on VEGF165 [7].


Localization (targets) of Flt-1 in endothelial cell
4) Confidence 0.71 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0.47 Pain Relevance 0.03
Although in vitro studies had found sVEGFR1, in both monomeric and dimeric forms, to be able to form complexes with VEGF in significant amounts in HUVEC-conditioned media [8], [10], there is currently no in vivo data on their relative quantities or the dimerization mechanism (whether some sVEGFR1 are secreted as homodimers or whether dimerization is ligand-dependent).
Localization (secreted) of sVEGFR1
5) Confidence 0.66 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Densities and VEGF-affinity of interstitial matrix sites affected only matrix-bound reservoirs of VEGF165 and sVEGFR1
Localization (reservoirs) of sVEGFR1 in reservoirs
6) Confidence 0.66 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
If luminal expression of VEGFR1 is considered in the future, luminal secretion of sVEGFR1 should be simultaneously investigated as well.
Localization (secretion) of sVEGFR1
7) Confidence 0.66 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0.08 Pain Relevance 0
1) for both VEGF and sVEGFR1 concentrations (Fig. 8A); increasing kL lessened VEGF gradients but steepened sVEGFR1 gradients (Fig. 9A); while decreasing kCL reduced VEGF gradients without much effect on sVEGFR1 gradients (Fig. 10).
Localization (concentrations) of sVEGFR1
8) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Fig. 3A illustrates the VEGF and sVEGFR1 responses to increasing sVEGFR1-secretion rates.
Localization (secretion) of sVEGFR1
9) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
The steady-state plasma and interstitial free sVEGFR1 concentrations ([sR1]pl, [sR1]IS) were then plotted over a range of sVEGFR1-secretion rates from the normal tissue and calf compartments (qsR1,Normal and qsR1,Calf) in Fig. 3A, while VEGF-secretion was fixed at qV,+Ctrl.
Localization (secretion) of sVEGFR1 in plasma
10) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Secondly, the transendothelial gradient of sVEGFR1 at control favored net extravasation, hence increasing kP resulted in: lower plasma concentrations of free sVEGFR1; as well as increased free sVEGFR1 in the interstitium facing the endothelium where kP was upregulated, at the expense of a decrease in interstitial free sVEGFR1 in the other tissue compartment (e.g., “Control” vs.
Localization (decrease) of sVEGFR1 in endothelium
11) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
This may suggest that hypoxia-induced secretion of sVEGFR1 (as opposed to lymphatic drainage of sVEFR1) is indeed the faster and major source of elevated plasma sVEGFR1 in exercise; but our simulations were unable to confirm the conclusion by Bailey et al. [49] that VEGF trapping by the surge of sVEGFR1 had caused the drop in plasma VEGF.
Localization (secretion) of sVEGFR1 in plasma associated with hypoxia
12) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0.23 Pain Relevance 0
We further showed that NRP1-dependent internalization of sVEGFR1 can be a major regulator of free sVEGFR1 levels in both interstitia and plasma, both directly (e.g., varying NRP1 densities) and indirectly (e.g., R2/R1 ratio and VEGF-VEGFR1 binding alter the availability of uncoupled NRP1s) (Fig. 5A, 6B).
Localization (internalization) of sVEGFR1 in plasma
13) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
At the control secretion rates of VEGF and sVEGFR1 needed to reproduce these selected plasma concentrations, our predicted interstitial concentrations ([V]IS?
Localization (secretion) of sVEGFR1 in plasma
14) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
The much lower complexed fractions from experimental data may indicate that in vivo, other soluble receptors (e.g., sVEGFR2, sNRP1, plasma fibronectin) can strongly compete with sVEGFR1 as plasma reservoirs for VEGF, or significant quantities of other ligands (e.g., PlGF, VEGF-B) are present to compete with VEGF for sVEGFR1 binding.
Localization (compete) of sVEGFR1 in plasma
15) Confidence 0.62 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Free sVEGFR1 was secreted abluminally from endothelial cells into the interstitial space (Fig. 1B); luminal secretion of sVEGFR1 was neglected in congruency with model assumptions to neglect luminal insertion of membrane-tethered VEGFRs (for which there is little quantitive evidence and will be separately investigated in further studies).
Localization (secreted) of sVEGFR1 in endothelial cells
16) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0.13 Pain Relevance 0.03
Such characterization proved useful in explaining VEGF/sVEGFR1 system responses observed in subsequent parameter sensitivity analyses of: the secretion rates of VEGF and sVEGFR1 (Results section 2); surface receptor densities (section 3); VEGF-affinities of surface receptors (section 4); VEGF-affinities of interstitial matrix sites (section 5); and transport parameters (section 6).


Localization (secretion) of sVEGFR1 in section 3
17) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0.03
Increasing VEGF- or sVEGFR1-secretion rates did not systemically lower free sVEGFR1 or free VEGF concentrations respectively

2.1.

Localization (secretion) of sVEGFR1
18) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
System sensitivity to sVEGFR1-secretion rates
Localization (secretion) of sVEGFR1
19) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
[sR1]IS,Normal and [sR1]IS,Calf were predicted to most significantly depend on their local sVEGFR1-secretion rates, qsR1,Normal and qsR1,Calf respectively, in a linear fashion.
Localization (secretion) of sVEGFR1
20) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0

General Comments

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