Flow-dependent regulation of angiopoietin-2.

Flow-dependent regulation of angiopoietin-2. Research Abstract Details 

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Flow-dependent regulation of angiopoietin-2. Abstract Text:

Winfried Goettsch,Corina Gryczka,Thomas Korff,Evelyn Ernst,Claudia Goettsch,Jochen Seebach,Hans-Joachim Schnittler,Hellmut G Augustin,Henning Morawietz,Winfried Goettsch,Corina Gryczka,Thomas Korff,Evelyn Ernst,Claudia Goettsch,Jochen Seebach,Hans-Joachim Schnittler,Hellmut G Augustin,Henning Morawietz,

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.

Flow-dependent regulation of angiopoietin-2. Publishing Authors By Initials

W Goettsch,C Gryczka,T Korff,E Ernst,C Goettsch,J Seebach,HJ Schnittler,HG Augustin,H Morawietz,W Goettsch,C Gryczka,T Korff,E Ernst,C Goettsch,J Seebach,HJ Schnittler,HG Augustin,H Morawietz,

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Flow-dependent regulation of angiopoietin-2. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of cellular physiology

VOLUME: 214

Page Numbers: 491-503

Journal Abbreviation: J. Cell. Physiol.

ISSN: 1097-4652

DAY: 27

MONTH: Feb

YEAR: 2008

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LANGUAGE: eng

NlmUniqueID: 50222

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AFFILIATION: Department of Vascular Endothelium and Microcirculation, University of Technology, Dresden, Germany.

Country: United States

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MEDLINETA: J Cell Physiol

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