| Flow-dependent regulation of angiopoietin-2. | |
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MedLine Citation:
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PMID: 17960565 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 214 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2007-11-27 Completed Date: 2007-12-26 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 491-503 Citation Subset: IM |
Copyright Information:
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(c) 2007 Wiley-Liss, Inc. |
Affiliation:
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Department of Vascular Endothelium and Microcirculation, University of Technology, Dresden, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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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:
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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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