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Aggretin elicited significant angiogenic effects in both in vivo and in vitro angiogenesis assays, and incubation of HUVECs with aggretin activated phosphatidylinositol 3-kinase (PI3K), Akt, and extracellular-regulated kinase 1\/2 (ERK1\/2); these effects were blocked by A2-IIE10 or vascular endothelial growth factor (VEGF) monoclonal antibody (mAb). The angiogenic effect induced by aggretin may be via the production of VEGF because the VEGF level was elevated and VEGF mAb pretreatment inhibited Akt\/ERK1\/2 activation as well as the in vivo angiogenesis induced by aggretin. The VEGF production induced by aggretin can be blocked by A2-IIE10 mAb pretreatment. In conclusion, aggretin induces endothelial cell proliferation, migration, and angiogenesis by interacting with integrin \u03b12\u03b21, leading to activation of PI3K, Akt, and ERK1\/2 pathways, and the increased expression of VEGF may be responsible for its angiogenic activity.<\/jats:p>","DOI":"10.1182\/blood-2003-07-2483","type":"journal-article","created":{"date-parts":[[2003,11,24]],"date-time":"2003-11-24T20:14:27Z","timestamp":1069704867000},"page":"2105-2113","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":45,"title":["Aggretin, a snake venom\u2013derived endothelial integrin \u03b12\u03b21 agonist, induces angiogenesis via expression of vascular endothelial growth factor"],"prefix":"10.1182","volume":"103","author":[{"given":"Ching-Hu","family":"Chung","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tur-Fu","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221542148500_REF1","doi-asserted-by":"crossref","unstructured":"Folkman J. 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