Thrombin induces angiogenesis and vascular endothelial growth factor expression in human endothelial cells: possible relevance to HIF-1alpha.
The serine protease thrombin present at the site of vascular injury triggers fibrin formation, platelet activation and different cellular responses including angiogenesis. We report a role for thrombin in the human monolayer cultured endothelial cell growth and angiogenesis in 3D collagen gel angiogenesis assay. The angiogenic activity of thrombin is, in part, related to the expression of the vascular endothelial growth factor (VEGF)165 mRNA, assessed by reverse transcriptase-polymerase chain reaction, either in monolayer cultured endothelial cells or in endothelial cells forming capillary-like structures in the 3D collagen gel assay. This expression of VEGF mRNA is associated with a VEGF secretion in the supernatant of thrombin-treated human umbilical vein endothelial cells. The thrombin-induced VEGF165 mRNA expression is associated with the regulation of hypoxia-inducible factor 1alpha, analyzed by Western Blot, in endothelial cells.
Dupuy
E
E
Institut des Vaisseaux et du Sang and INSERM U348, Hôpital Lariboisière, Paris, France. evelyne.dupuy@lrb.ap-hop-paris.fr
Habib
A
A
Lebret
M
M
Yang
R
R
Levy-Toledano
S
S
Tobelem
G
G
D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology* / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D013917:Thrombin