Angiopoietin 2 induces cell cycle arrest in endothelial cells: a possible mechanism involved in advanced plaque neovascularization
To characterize the molecules and the mechanisms regulating the neoangiogenetic process in advanced atherosclerotic plaques. Western blot and immunofluorescence analysis of atherosclerotic specimens demonstrated that unlike neovessels from early lesions that expressed vascular endothelial growth fac...
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| Vydáno v: | Arteriosclerosis, thrombosis, and vascular biology Ročník 24; číslo 3; s. 511 |
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| Hlavní autoři: | , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
01.03.2004
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| Témata: | |
| ISSN: | 1524-4636, 1524-4636 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
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| Shrnutí: | To characterize the molecules and the mechanisms regulating the neoangiogenetic process in advanced atherosclerotic plaques.
Western blot and immunofluorescence analysis of atherosclerotic specimens demonstrated that unlike neovessels from early lesions that expressed vascular endothelial growth factor (VEGF) and angiopoietin1 (Angio1), vessels from advanced lesions expressed VEGF and angiopoietin 2 (Angio2). Moreover, only few neovessels from advanced lesions showed a positive immunostaining for proliferating cell nuclear antigen. Angio1-elicited and Angio2-elicited intracellular events in endothelial cells (EC) demonstrated that while Angio1 triggered Erk1/Erk2 mitogen activated protein kinases (MAPK) and Akt activation, Angio2 (50 ng/mL) induced STAT5 activation and p21waf expression and increased the fraction of cells in G1. Both Angio2-mediated events were abrogated by expressing a dominant negative STAT5 construct (DeltaSTAT5). Consistent with the expression of Angio2 in neovessels of advanced lesions a transcriptionally active STAT5 was detected. Moreover, co-immunoprecipitation experiments revealed the presence of a STAT5/Tie2 molecular complex in neointima vessels from advanced, but not from early, lesions.
In advanced lesions, the activation of the Tie2-mediated STAT5 signaling pathway may negatively regulate vessel growth. |
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| Bibliografie: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
| ISSN: | 1524-4636 1524-4636 |
| DOI: | 10.1161/01.ATV.0000116864.86607.35 |