{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:53:19Z","timestamp":1787503999659,"version":"build-2736575974"},"reference-count":41,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Vasc Res"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background\/Aims:&lt;\/i&gt;&lt;\/b&gt; Venous neointimal hyperplasia (NH) is the predominant cause of stenosis in hemodialysis arteriovenous grafts (AVG), but there is currently no clinically used therapy to prevent NH. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; A porcine AVG model was used to identify potential pharmacological targets to prevent NH. Sunitinib, a broad-spectrum tyrosine kinase inhibitor, was examined as a potential anti-NH drug utilizing in vitro and ex vivo models. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; In an in vivo porcine model, PDGF, VEGF and their receptors PDGFR-\u03b1 and VEGFR-2 were upregulated at the venous anastomosis within 2 weeks after AVG placement, with NH development by 4 weeks. Sunitinib inhibited PDGF-stimulated proliferation, migration, phosphorylation of MAPK and PI3K\/Akt proteins and changes in the expression of cell-cycle regulatory proteins in vascular smooth-muscle cells as well as VEGF-stimulated endothelial cell proliferation in vitro. In an ex vivo model, significant NH was observed in porcine vein segments perfused for 12 days under pathological shear stress. Sunitinib (100 n&lt;smlcap&gt;M&lt;\/smlcap&gt;) inhibited NH formation, with the intima-to-lumen area ratio decreasing from 0.45 \u00b1 0.25 to 0.04 \u00b1 0.02 (p &lt; 0.05) with treatment. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; These findings demonstrate sunitinib to be a potential NH-preventive drug as well as the utility of an ex vivo model to investigate pharmacotherapies under pathophysiological flow conditions.<\/jats:p>","DOI":"10.1159\/000442977","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T17:02:41Z","timestamp":1453309361000},"page":"244-256","source":"Crossref","is-referenced-by-count":6,"title":["Prevention of Venous Neointimal Hyperplasia by a Multitarget Receptor Tyrosine Kinase Inhibitor"],"prefix":"10.1159","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8740-1509","authenticated-orcid":false,"given":"Sun 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