Document Detail


Flow-dependent regulation of angiopoietin-2.
MedLine Citation:
PMID:  17960565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelial cells are constantly exposed to high or low shear stress in arteries and veins by the flowing blood. Angiopoietin-2 (Ang-2) is acting as a critical regulator of vessel maturation and endothelial cell quiescence. In this study, flow-dependent regulation of Ang-2 was analyzed in vitro and in vivo. Ang-2 mRNA, protein expression and release was upregulated by 24 h of low (1 dyne/cm(2)), but downregulated by high flow (30 dyne/cm(2)) in human endothelial cells. Increased endothelial NO synthase expression and NO formation was not affecting regulation of Ang-2 by low or high flow. Low and high flow increased VEGF-A expression. Inhibition of VEGFR-2 prevented upregulation of Ang-2 by low flow, but not downregulation of Ang-2 by high flow. Furthermore, upregulation of Ang-2 by VEGF was reduced by application of high flow. Forkhead box O (FOXO) transcription factor FOXO1 has been shown to regulate Ang-2 expression in endothelial cells. FOXO1 binding activity was reduced by high flow. Nuclear localization of transcription factor FOXO1 was not changed by low flow, but reduced by high flow. In vivo, Ang-2 was higher expressed in veins compared to arteries. Arterial ligation augmented Ang-2 expression in distal arterial low flow areas. Our results support a VEGF-dependent induction of Ang-2 in low flow areas, and FOXO1-dependent downregulation of Ang-2 in high flow areas. These data suggest a new mechanism of flow-dependent regulation of vessel stability and differentiation.
Authors:
Winfried Goettsch; Corina Gryczka; Thomas Korff; Evelyn Ernst; Claudia Goettsch; Jochen Seebach; Hans-Joachim Schnittler; Hellmut G Augustin; Henning Morawietz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  214     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2007-11-27     Completed Date:  2007-12-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  491-503     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Affiliation:
Department of Vascular Endothelium and Microcirculation, University of Technology, Dresden, Germany.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors
Angiopoietin-1 / pharmacology
Angiopoietin-2 / metabolism,  secretion*
Animals
Benzoquinones / pharmacology
Cell Separation / methods
Cells, Cultured
Chromones / pharmacology
Culture Media, Serum-Free
Dactinomycin / pharmacology
Endothelium, Vascular / drug effects,  metabolism*
Femoral Artery / physiology*
Forkhead Transcription Factors / analysis,  metabolism
Gene Expression Regulation*
Humans
Lactams, Macrocyclic / pharmacology
Male
Mice
Mice, Inbred C57BL
Morpholines / pharmacology
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / analysis
Nitric Oxide Synthase Type III / antagonists & inhibitors
Nitrites / analysis
Protein-Tyrosine Kinases / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / analysis,  metabolism
RNA, Messenger / analysis
Receptor, TIE-2 / metabolism
Regional Blood Flow
Signal Transduction / drug effects
Stress, Mechanical
Triazenes / pharmacology
Umbilical Veins / cytology
Vascular Endothelial Growth Factor A / pharmacology
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; 0/Angiopoietin-1; 0/Angiopoietin-2; 0/Benzoquinones; 0/Chromones; 0/Culture Media, Serum-Free; 0/FOXO1 protein, human; 0/Forkhead Transcription Factors; 0/Lactams, Macrocyclic; 0/Morpholines; 0/Nitrites; 0/RNA, Messenger; 0/Triazenes; 0/Vascular Endothelial Growth Factor A; 10102-43-9/Nitric Oxide; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 50-76-0/Dactinomycin; 50903-99-6/NG-Nitroarginine Methyl Ester; 70563-58-5/herbimycin; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, TIE-2; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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