|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
2001-9-10
|
|
pubmed:abstractText |
The known responses of vascular endothelial growth factor (VEGF) are mediated through VEGF receptor-2 (VEGFR-2/KDR) in endothelial cells. However, it is unknown whether VEGFR-1 (Flt-1) is an inert decoy or a signaling receptor for VEGF during physiological or pathological angiogenesis. Here we report that VEGF-stimulated nitric oxide (NO) release is inhibited by blockade of VEGFR-1 and that VEGFR-1 via NO negatively regulates of VEGFR-2-mediated proliferation and promotes formation of capillary networks in human umbilical vein endothelial cells (HUVECs). Inhibition of VEGFR-1 in a murine Matrigel angiogenesis assay induced large aneurysm-like structures. VEGF-induced capillary growth over 14 days was inhibited by anti-VEGFR-2-blocking antibody as determined by reduced tube length between capillary connections (P < 0.0001) in an in vitro angiogenesis assay. In contrast, loss of VEGFR-1 activity with a neutralizing anti-VEGFR-1 antibody resulted in an increase in the accumulation of endothelial cells (P < 0.0001) and a dramatic decrease in the number of capillary connections that were restored by the addition of NO donor. Porcine aortic endothelial (PAE) cells expressing human VEGFR-1 but not VEGFR-2 plated on growth factor-reduced Matrigel rearranged into tube-like structures that were prevented by anti-VEGFR-1 antibody or a cGMP inhibitor. VEGF stimulated NO release from VEGFR-1- but not VEGFR-2-transfected endothelial cells and placenta growth factor-1 stimulated NO release in HUVECs. Blockade of VEGFR-1 increased VEGF-mediated HUVEC proliferation that was inhibited by NO donors, and potentiated by NO synthase inhibitors. These data indicate that VEGFR-1 is a signaling receptor that promotes endothelial cell differentiation into vascular tubes, in part by limiting VEGFR-2-mediated endothelial cell proliferation via NO, which seems to be a molecular switch for endothelial cell differentiation.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10022836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10068204,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10323857,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10338370,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10357944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10551875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10600473,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10747927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-10815805,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-11103941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-11141500,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-11221852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-1279183,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-1320711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-1380254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-6253831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-7525653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-7596435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-7596436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-7803624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-7824266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-7929439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-7962111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-8148155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-8557695,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-8621410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-8663424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9034784,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9131263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9169492,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9180894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9186585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9194854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9256279,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9399960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9443437,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9598598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9616228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9632135,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9689083,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9776730,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11549592-9872925
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/NOS3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroso Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Penicillamine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vascular Endothelial...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
0002-9440
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
159
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
993-1008
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:11549592-Humans,
pubmed-meshheading:11549592-Nitric Oxide,
pubmed-meshheading:11549592-Nitroso Compounds,
pubmed-meshheading:11549592-Cell Division,
pubmed-meshheading:11549592-Penicillamine,
pubmed-meshheading:11549592-Cells, Cultured,
pubmed-meshheading:11549592-Endothelium, Vascular,
pubmed-meshheading:11549592-Lymphokines,
pubmed-meshheading:11549592-Protein Isoforms,
pubmed-meshheading:11549592-Transfection,
pubmed-meshheading:11549592-Neovascularization, Physiologic,
pubmed-meshheading:11549592-Vascular Endothelial Growth Factor A,
pubmed-meshheading:11549592-Vascular Endothelial Growth Factors
|
