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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Veröffentlicht in:	Arteriosclerosis, thrombosis, and vascular biology Jg. 24; H. 3; S. 511
Hauptverfasser:	Calvi, Cristina, Dentelli, Patrizia, Pagano, Marco, Rosso, Arturo, Pegoraro, Marco, Giunti, Sara, Garbarino, Giovanni, Camussi, Giovanni, Pegoraro, Luigi, Brizzi, Maria Felice
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.03.2004
Schlagworte:	Angiopoietin-1 - biosynthesis Angiopoietin-1 - genetics Angiopoietin-1 - physiology Angiopoietin-2 - biosynthesis Angiopoietin-2 - genetics Angiopoietin-2 - pharmacology Angiopoietin-2 - physiology Arteriosclerosis - pathology Carotid Arteries - metabolism Carotid Arteries - pathology Carotid Artery Diseases - pathology Cell Cycle - drug effects Cell Cycle Proteins - biosynthesis Cell Cycle Proteins - genetics Cell Line, Tumor - metabolism Cells, Cultured - drug effects Cells, Cultured - metabolism Coronary Artery Disease - pathology Coronary Vessels - metabolism Coronary Vessels - pathology Cyclin-Dependent Kinase Inhibitor p21 Disease Progression DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Endothelial Cells - cytology Endothelial Cells - drug effects Endothelium, Vascular - pathology G1 Phase - drug effects Gene Expression Regulation - drug effects Gene Expression Regulation - physiology Humans Macromolecular Substances Milk Proteins - genetics Neovascularization, Physiologic - drug effects Neovascularization, Physiologic - physiology Proliferating Cell Nuclear Antigen - biosynthesis Proliferating Cell Nuclear Antigen - genetics Receptor, TIE-2 - physiology Signal Transduction - drug effects STAT5 Transcription Factor Trans-Activators - genetics Trans-Activators - physiology Transcription, Genetic Transfection Tunica Intima - pathology
ISSN:	1524-4636, 1524-4636
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Zusammenfassung:	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.
Bibliographie:	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