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Karger AG","issue":"6","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"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":[[2014]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;\/i&gt;&lt;\/b&gt; Phenotypic switch of vascular smooth muscle cells (VSMCs) accompanies neointima formation and associates with vascular diseases. Platelet-derived growth factor (PDGF)-induced activation of PDGFR\/Akt1 and \u03b2-catenin signaling pathways in VSMCs has been implicated in vessel occlusion. Transglutaminase 2 (TG2) regulates these pathways and its levels are increased in the neointima. &lt;b&gt;&lt;i&gt;Objective:&lt;\/i&gt;&lt;\/b&gt; The aim of this study was to evaluate the role of TG2 in PDGF\/\u03b2-catenin signaling cross-talk and assess its contribution to neointima. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Aortic VSMCs from wild-type and TG2 knockout mice were tested in vitro for levels of VSMC markers, proliferation, migration and PDGF-induced activation of PDGFR\/Akt1 and \u03b2-catenin pathways. Neointima in these mice was studied ex vivo in coronary vessels using a heart slice model and in vivo using a carotid artery ligation model. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Genetic deletion of TG2 attenuated the PDGF-induced phenotypic switch of aortic VSMCs, reduced their proliferation and migration rates, and inhibited PDGF-induced activation of PDGFR\/Akt1 and \u03b2-catenin pathways in both ex vivo and in vivo neointima models. Importantly, genetic deletion of TG2 also markedly attenuated vessel occlusion. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; TG2 promotes neointima formation by mediating the PDGF-induced activation of the PDGFR\/Akt1 and \u03b2-catenin pathways in VSMCs. This study identifies TG2 as a potential therapeutic target for blocking neointima in blood vessels.<\/jats:p>","DOI":"10.1159\/000369461","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T08:58:32Z","timestamp":1422003512000},"page":"418-428","source":"Crossref","is-referenced-by-count":18,"title":["Transglutaminase 2 Promotes PDGF-Mediated Activation of PDGFR\/Akt1 and \u03b2-Catenin Signaling in Vascular Smooth Muscle Cells and Supports Neointima Formation"],"prefix":"10.1159","volume":"51","author":[{"given":"Maria","family":"Nurminskaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Beazley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth P.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey 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