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In previous studies, we demonstrated that aggretin, a heterodimeric snake venom C-type lectin, exhibits pro-angiogenic activities via integrin \u03b12\u03b21 ligation. We hypothesised that small-mass aggretin fragments may bind integrin \u03b12\u03b21 and act as antagonists of angiogenesis. In this study, the anti-angiogenic efficacy of a synthesised aggretin \u03b1-chain C-terminus (AACT, residue 106\u2013136) was evaluated in both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> angiogenesis models. The AACT demonstrated inhibitory effects on collagen-induced platelet aggregation and HUVEC adhesion to immobilised collagen. These results indicated that AACT may block integrin \u03b12\u03b21\u2212collagen interaction. AACT also inhibited HUVEC migration and tube formation. Aortic ring sprouting and Matrigel implant models demonstrated that AACT markedly inhibited VEGF-induced neovascularisation. In addition, induction of FAK\/PI3K\/ERK1\/2 tyrosine phosphorylation and talin 1\/2 associated with integrin \u03b21 which are induced by VEGF were blocked by AACT. Similarly, tyrosine phosphorylation of VEFGR2 and ERK1\/2 induced by VEGF was diminished in integrin \u03b12-silenced endothelial cells. Our results demonstrate that AACT is a potential therapeutic candidate for angiogenesis related-diseases via integrin \u03b12\u03b21 blockade.<\/jats:p>","DOI":"10.1038\/srep43612","type":"journal-article","created":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T15:37:12Z","timestamp":1488469032000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Aggretin Venom Polypeptide as a Novel Anti-angiogenesis Agent by Targeting Integrin alpha2beta1"],"prefix":"10.1038","volume":"7","author":[{"given":"Ching Hu","family":"Chung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien Hsin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun Chieh","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kung Tin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui Chin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tur Fu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,3,2]]},"reference":[{"key":"BFsrep43612_CR1","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1056\/NEJM199512283332608","volume":"333","author":"J Folkman","year":"1995","unstructured":"Folkman, J. 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