| Title | Validation of protease-activated receptor-1 as a target for developing anti-angiogenic agents | |
| Authors | Panagiota Zania, Sosanna Kritikou, Christodoulos S. Flordellis, Michael E. Maragoudakis and Nikos E. Tsopanoglou
Department of Pharmacology, Medical School, University of Patras, 26500 Patras, Greece |
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| Citation | Zania, P., Kritikou, S., Flordellis, Ch.S., Maragoudakis, M.E., Tsopanoglou, N.E.: Validation of protease-activated receptor-1 as a target for developing anti-angiogenic agents, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 355-357 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | Angiogenesis, PAR-1 antagonists, endothelial cell proliferation, apoptosis. | |
| Other Terms | review article | |
| Summary | In this study we evaluated the effects of two PAR-1 selective antagonists, SCH79797 and RWJ56110, in the angiogenic cascade. These antagonists suppressed both the basic angiogenesis and that stimulated by thrombin in the chick chorioallantoic membrane model in vivo and tube formation in the in vitro Matrigel system. These effects were dose-dependent and well correlated with the inhibitory effects of SCH79797 and RWJ56110 on primary endothelial cell proliferation and on the initiation of apoptosis. PAR-1 blockage resulted in inhibition of endothelial cell growth by increasing the sub-G0/G1 fraction and reducing the percentage of cells in the S-phase. Consistent with this, PAR-1 antagonists reduced incorporation of [3H]-thymidine in endothelial cells and blocked the phosphorylation of extracellular signal-regulated kinases. Analysis by Annexin V/propidium iodide staining and poly(ADPribose)polymerase cleavage revealed that PAR-1 blockage increased apoptotic cell death via caspases. | |
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| Relative Papers |
Online ISSN 1011-6575
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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