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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2105-2113. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-07-2483. This Article Full Text (PDF) All Versions of this Article: 2003-07-2483v1 103/6/2105    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chung, C.-H. Articles by Huang, T.-F. Search for Related Content PubMed PubMed Citation Articles by Chung, C.-H. Articles by Huang, T.-F. Social Bookmarking                   What's this? Submitted July 24, 2003 Accepted October 31, 2003 Aggretin, a snake venom-derived endothelial integrin 21 agonist, induces angiogenesis via expression of vascular endothelial growth factor Ching-Hu Chung, Wen-Bin Wu, and Tur-Fu Huang* Department of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan * Corresponding author; email: turfu{at}ccms.ntu.edu.tw.. Aggretin, a collagen-like 21 agonist purified from Calloselasma rhodostoma venom, was shown to increase human umbilical vein endothelial cell (HUVEC) proliferation and HUVECs migration toward immobilized aggretin was also increased. These effects were blocked by A2-IIE10, an antibody raised against integrin 2. Aggretin bound to HUVEC in a dose-dependent and saturable manner, which was specifically inhibited by A2-IIE10, as examined by flow cytometry. Aggretin elicited significant angiogenic effects both in vivo and in vitro angiogenesis assays, and incubation of HUVECs with aggretin activated phosphatidylinositol 3-kinase (PI3K), Akt and extracellular regulated kinase (ERK1/2), these effects were blocked by A2-IIE10 or vascular endothelial growth factor (VEGF) mAb. The angiogenic effect induced by aggretin may be via the production of VEGF, since VEGF level was elevated and VEGF mAb pretreatment was able to inhibit Akt/ERK1/2 activation as well as the in vivo angiogenesis induced by aggretin. The VEGF production induced by aggretin can be blocked by AII-2E10 mAb pretreatment. In conclusion, aggretin induces endothelial cell proliferation, migration and angiogenesis by interacting with integrin 21, leading to activation of PI3K, Akt and ERK1/2 pathways, and the increased expression of VEGF may be responsible for its angiogenic activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Sun and K. R. McCrae Endothelial-cell apoptosis induced by cleaved high-molecular-weight kininogen (HKa) is matrix dependent and requires the generation of reactive oxygen species Blood, June 15, 2006; 107(12): 4714 - 4720. [Abstract] [Full Text] [PDF] K. Suzuki-Inoue, G. L. J. Fuller, A. Garcia, J. A. Eble, S. Pohlmann, O. Inoue, T. K. Gartner, S. C. Hughan, A. C. Pearce, G. D. Laing, et al. A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2 Blood, January 15, 2006; 107(2): 542 - 549. [Abstract] [Full Text] [PDF]

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