Inhibition of Angiogenic Properties of Brain Endothelial Cells by Platelet-Derived Sphingosine-1-Phosphate

The platelet-derived lysophospholipid sphingosine-1-phosphate (S1P) is present in blood plasma and is one of the most potent growth factors displaying proangiogenic activity towards endothelial cells (EC) derived from various tissues. The paracrine regulation of brain angiogenesis by platelet-derive...

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Veröffentlicht in:Journal of cerebral blood flow and metabolism 2005-09, Vol.25 (9), p.1171-1182
Hauptverfasser: Pilorget, Anthony, Annabi, Borhane, Bouzeghrane, Fatiha, Marvaldi, Jacques, Luis, José, Béliveau, Richard
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container_end_page 1182
container_issue 9
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container_title Journal of cerebral blood flow and metabolism
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creator Pilorget, Anthony
Annabi, Borhane
Bouzeghrane, Fatiha
Marvaldi, Jacques
Luis, José
Béliveau, Richard
description The platelet-derived lysophospholipid sphingosine-1-phosphate (S1P) is present in blood plasma and is one of the most potent growth factors displaying proangiogenic activity towards endothelial cells (EC) derived from various tissues. The paracrine regulation of brain angiogenesis by platelet-derived growth factors is, however, poorly understood. In the present study, we assessed the role of S1P on brain EC migration and tubulogenesis, using rat brain-derived (RBE4) EC as an in vitro model. We show that S1P inhibits brain EC migration and tubulogenesis, while it displays proangiogenic activity towards noncerebral EC. Overexpression of the S1P receptor S1P-1 in RBE4 cells potentiated all of the S1P-mediated events. We also show that the lack of expression of MT1-MMP, a membrane-bound matrix metalloproteinase that is thought to cooperate with S1P in tubulogenic processes, may explain the antiangiogenic activity of S1P on brain vasculature. Altogether our results support the hypothesis of a tissue-specific, antiangiogenic role of S1P in the brain, which may help to stabilize the cerebral vasculature and thus have crucial impact on the setting and regulation of normal brain vascularization.
doi_str_mv 10.1038/sj.jcbfm.9600117
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subjects Animals
Biological and medical sciences
Blood Platelets - chemistry
Blotting, Western
Cell Adhesion
Cell Differentiation - drug effects
Cell Movement
Cells, Cultured
Culture Media
DNA, Complementary - biosynthesis
DNA, Complementary - genetics
Endothelial Cells - drug effects
Endothelial Cells - ultrastructure
Growth Substances - pharmacology
Humans
Investigative techniques, diagnostic techniques (general aspects)
Lysophospholipids - blood
Lysophospholipids - pharmacology
Matrix Metalloproteinase 1 - metabolism
Medical sciences
Neovascularization, Physiologic - drug effects
Nervous system
Neurology
Neuropharmacology
Neuroprotective agent
Oligonucleotides, Antisense - pharmacology
Pharmacology. Drug treatments
Rats
Reverse Transcriptase Polymerase Chain Reaction
RNA - biosynthesis
RNA - isolation & purification
Sphingosine - analogs & derivatives
Sphingosine - blood
Sphingosine - pharmacology
Transfection
Ultrasonic investigative techniques
Vascular diseases and vascular malformations of the nervous system
title Inhibition of Angiogenic Properties of Brain Endothelial Cells by Platelet-Derived Sphingosine-1-Phosphate
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