Document Detail


Cyclical mechanical stretch enhances angiopoietin-2 and Tie2 receptor expression in cultured human umbilical vein endothelial cells.
MedLine Citation:
PMID:  12653688     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelial cells are essential for neovascularization. Angiopoietins and Tie receptors are required for a normal vasculature. How cyclical mechanical stretch affects the expression of components of the angiopoietin system is not known. In this study, we investigated the regulation of angiopoietins and Tie receptors by cyclical mechanical stretch in cultured human umbilical vein endothelial cells (HUVECs). HUVECs grown on a flexible membrane base were stretched by vacuum to 20% elongation, at 60 cycles/min. The levels of angiopoietin-2 protein began to increase as early as 2 h after stretch was initially applied, reached a maximum of 2.7-fold over the control value by 6 h. The Tie2 receptor protein showed the same pattern as Ang-2. These increases in angiopoietin-2 and Tie2 receptor proteins at 6 h were blocked by the addition (30 min before stretch) of the protein kinase C inhibitor Gö6976 (16 nM) or the tyrosine kinase inhibitor herbimycin A (24 microM). Similar to protein expression, the levels of angiopoietin-2 and Tie2 receptor mRNAs in HUVECs increased 3.1-fold and 2.5-fold respectively after stretch for 6 h. These increases were also blocked by Gö6976 or herbimycin A. Cyclical mechanical stretch increased (and Gö6976 or herbimycin A abrogated these increases) the immunohistochemical labelling of angiopoietin-2 and Tie2 receptor after a 6 h stretch. The levels of angiopoietin-1 and Tie1 receptor proteins, mRNAs and immunohistochemical staining were unaffected by cyclical mechanical stretch. Thus cyclical mechanical stretch activates the expression of angiopoietin-2 and the Tie2 receptor, but not angiopoietin-1 or the Tie1 receptor, in cultured HUVECs. This mechanical effect is probably mediated by the tyrosine kinase and protein kinase C pathways.
Authors:
Hang Chang; Bao-Wei Wang; Peiliang Kuan; Kou-Gi Shyu
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  104     ISSN:  0143-5221     ISO Abbreviation:  Clin. Sci.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-03-25     Completed Date:  2003-07-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  421-8     Citation Subset:  IM    
Affiliation:
The Department of Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inducing Agents / analysis,  metabolism*
Angiopoietin-2
Benzoquinones
Blotting, Western / methods
Carbazoles / pharmacology
Endothelium, Vascular / physiopathology*
Humans
Immunohistochemistry / methods
Indoles / pharmacology
Lactams, Macrocyclic
Neoplasm Proteins / analysis,  metabolism*
Protein Kinase C / antagonists & inhibitors
Protein-Tyrosine Kinases / antagonists & inhibitors
Proto-Oncogene Proteins*
Quinones / pharmacology
Receptor, TIE-2
Reverse Transcriptase Polymerase Chain Reaction
Stress, Mechanical
Time Factors
Umbilical Veins
Chemical
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Angiopoietin-2; 0/Benzoquinones; 0/Carbazoles; 0/Indoles; 0/Lactams, Macrocyclic; 0/MEN1 protein, human; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins; 0/Quinones; 136194-77-9/Go 6976; 70563-58-5/herbimycin; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, TIE-2; EC 2.7.11.13/Protein Kinase C

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