{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:37:18Z","timestamp":1753871838208,"version":"3.41.2"},"reference-count":19,"publisher":"Portland Press Ltd.","issue":"6","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":966,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Coronary artery disease is treated by vein grafting and stent implantation. Late vein graft failure and restenosis of stented arteries reduce the success rates of these approaches and are caused by neointima formation. We have previously shown that Wnt proteins are up-regulated during intimal thickening, and have speculated that these lead to activation of downstream genes with \u03b2-catenin\/T-cell factor (TCF)-responsive promoters. In the present study, we aimed to provide evidence that \u03b2-catenin\/TCF signalling promotes neointima formation and assess whether targeting this pathway has potential for reducing neointima formation. We utilized a gene therapy approach selectively targeting cells in which the \u03b2-catenin\/TCF pathway is activated by using a recombinant adenovirus Ad-TOPTK, which carries a herpes simplex virus thymidine kinase (HSV-TK) gene under the control of a \u03b2-catenin\/TCF-response promoter. Cells with activated \u03b2-catenin will therefore be selectively killed. Ad-TOPTK and ganciclovir (GCV) treatment significantly suppressed the growth of the neointima in a murine model of left carotid artery ligation. In summary, we demonstrated that Wnt\/\u03b2-catenin\/TCF signalling promotes neointima formation, by showing that the selective death of cells with activated \u03b2-catenin suppressed neointima formation. This highlights the therapeutic potential for reducing late vein graft failure and in-stent restenosis by targeting \u03b2-catenin\/TCF signalling.<\/jats:p>","DOI":"10.1042\/bsr20160229","type":"journal-article","created":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T01:40:45Z","timestamp":1478310045000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Suppression of neointima formation by targeting \u03b2-catenin\/TCF pathway"],"prefix":"10.1042","volume":"36","author":[{"given":"Helen","family":"Williams","sequence":"first","affiliation":[{"name":"School of Clinical Sciences, Research Floor Level 7, Bristol Royal Infirmary, Upper Maudlin St, Bristol BS2 8HW, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadie","family":"Slater","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, Research Floor Level 7, Bristol Royal Infirmary, Upper Maudlin St, Bristol BS2 8HW, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah\u00a0Jane","family":"George","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, Research Floor Level 7, Bristol Royal Infirmary, Upper Maudlin St, Bristol BS2 8HW, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2016,12,9]]},"reference":[{"key":"2021111618375420400_B1","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1016\/j.atherosclerosis.2010.08.033","article-title":"WNT\/beta-catenin signalling regulates intimal thickening and smooth muscle cell migration","volume":"213","author":"Williams","year":"2010","journal-title":"Atherosclerosis"},{"key":"2021111618375420400_B2","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1161\/ATVBAHA.116.307626","article-title":"Wnt2 and WISP-1\/CCN4 induce intimal thickening via promotion of smooth muscle cell migration","volume":"36","author":"Williams","year":"2016","journal-title":"Arterioscler. 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