Involvement of RhoA/Rho Kinase Signaling in VEGF-Induced Endothelial Cell Migration and Angiogenesis In Vitro
| Autor: | Pieter Koolwijk, Victor W.M. van Hinsbergh, Amanda M. G. Versteilen, Geerten P. van Nieuw Amerongen |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A rho GTP-Binding Proteins Umbilical Veins RHOA Pyridines Angiogenesis Cell Culture Techniques Neovascularization Physiologic Endothelial Growth Factors Biology chemistry.chemical_compound Cell Movement Humans Enzyme Inhibitors Rho-associated protein kinase Cells Cultured Cytoskeleton Fibrin Lymphokines Vascular Endothelial Growth Factors Amides Capillaries Cell biology Enzyme Activation Y-27632 Vascular endothelial growth factor Endothelial stem cell Vascular endothelial growth factor A chemistry biology.protein Intercellular Signaling Peptides and Proteins Endothelium Vascular Signal transduction rhoA GTP-Binding Protein Cardiology and Cardiovascular Medicine Penis Signal Transduction |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 23:211-217 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000054198.68894.88 |
| Popis: | Objective - Growth factor-induced angiogenesis involves migration of endothelial cells (ECs) into perivascular areas and requires active remodeling of the endothelial F-actin cytoskeleton. The small GTPase RhoA previously has been implicated in vascular endothelial growth factor (VEGF)-induced signaling pathways, but its role has not been clarified. Methods and Results - VEGF induced the activation of RhoA and recruited RhoA to the cell membrane of human ECs. This increase in RhoA activity is necessary for the VEGF-induced reorganization of the F-actin cytoskeleton, as demonstrated by adenoviral transfection of dominant-negative RhoA. Rho kinase mediated this effect of RhoA, as was demonstrated by the use of Y-27632, a specific inhibitor of Rho kinase. Inhibition of Rho kinase prevented the VEGF-enhanced EC migration in response to mechanical wounding but had no effect on basal EC migration. Furthermore, in an in vitro model for angiogenesis, inhibition of either RhoA or Rho kinase attenuated the VEGF-mediated ingrowth of ECs in a 3-dimensional fibrin matrix. Conclusions - VEGF-induced cytoskeletal changes in ECs require RhoA and Rho kinase, and activation of RhoA/Rho kinase signaling is involved in the VEGF-induced in vitro EC migration and angiogenesis. Chemicals/CAS: 4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide, 146986-50-7; F actin, 39409-31-9; fibrin, 9001-31-4; guanosine triphosphatase, 9059-32-9; vasculotropin, 127464-60-2; Amides; Endothelial Growth Factors; Enzyme Inhibitors; Fibrin, 9001-31-4; Intercellular Signaling Peptides and Proteins; Lymphokines; Pyridines; rho GTP-Binding Proteins, EC 3.6.5.2; rhoA GTP-Binding Protein, EC 3.6.5.2; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Y 27632, 138381-45-0 |
| Databáze: | OpenAIRE |
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