{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:34:26Z","timestamp":1784190866659,"version":"3.55.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Vascular leakage due to compromised integrity of the endothelial barrier is closely associated with brain damage in several neurological disorders, including ischaemic stroke. Saxatilin, a snake venom disintegrin containing the Arg-Gly-Asp (RGD) motif, exerts thrombolytic and antiplatelet effects by interacting with multiple integrins on platelets. Integrin signalling is indispensable for regulation of endothelial permeability. Saxatilin may play a role in vascular leakage after ischaemia because it has high affinity for endothelial integrins. Here, we determined whether Fc-saxatilin, an Fc-fusion protein of saxatilin, could prevent vascular leakage under hypoxic or ischaemic conditions. In mouse brain microvascular endothelial cells, hypoxia increased the permeability to FITC-dextran, and this effect was attenuated by Fc-saxatilin treatment. Fc-saxatilin also blocked vascular leakage of Evans Blue in the ischaemic brain induced by middle cerebral artery occlusion in mice. Furthermore, the expression of occludin, a tight junction protein, was reduced by hypoxia in endothelial cells. This downregulation of occludin was attenuated by Fc-saxatilin treatment. We also determined the activity of matrix metalloproteinases (MMPs) 2 and 9 because they are implicated in the degradation of occludin and of the microvascular basal lamina. Hypoxia increased MMP-9 activity, and this increase was attenuated by Fc-saxatilin treatment. Fc-saxatilin specifically bound to integrin \u03b1v\u03b23 of the endothelial cells and inhibited hypoxia-induced activation of FAK, a downstream signalling molecule in integrin-dependent signal transduction. Taken together, these results provide new insights into the mechanism via which Fc-saxatilin, as an integrin antagonist, prevents vascular leakage under ischemic conditions by regulating occludin expression in endothelial tight junctions.<\/jats:p><jats:p>Supplementary Material to this article is available online at www.thrombosis-online.com.<\/jats:p>","DOI":"10.1160\/th16-06-0469","type":"journal-article","created":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T09:55:13Z","timestamp":1482400513000},"page":"595-605","source":"Crossref","is-referenced-by-count":5,"title":["Fc-saxatilin suppresses hypoxia-induced vascular leakage by regulating endothelial occludin expression"],"prefix":"10.1160","volume":"117","author":[{"given":"Hyun-Jung","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il","family":"Kwon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Eun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayoung","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunho","family":"An","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungsoo","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Yu","family":"Hong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo 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