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Exploring novel approaches to prevent neointimal hyperplasia is important. MicroRNA\u2010146a (miR\u2010146a) plays an essential role in promoting vascular smooth muscle cell (VSMC) proliferation. Thus, the aim of the present study is to investigate whether adenovirus\u2010mediated miR\u2010146a sponge (Ad\u2010miR\u2010146a\u2010SP) gene therapy could attenuate neointimal formation in rat vein grafts. (Ad\u2010miR\u2010146a\u2010SP) was constructed to transfect cultured VSMCs and grafted veins. To improve the efficiency of transferring the miR\u2010146a sponge gene into the grafted veins, 20% poloxamer F\u2010127 gel incorporated with 0.25% trypsin was used to increase adenovirus contact time and penetration. miR\u2010146a\u2010SP transduction significantly reduced the expression of miR\u2010146a both in cultured VSMCs and vein grafts. miR\u2010146a sponge markedly attenuated VSMC proliferation and migration. Consistent with this, miR\u2010146a sponge gene therapy significantly attenuated neointimal formation and also improved blood flow in the vein grafts. Mechanistically, we identified the Kr\u00fcppel\u2010like factor 4(KLF4) as a potential downstream target gene of miR\u2010146a in vein grafts. Our data show that miR\u2010146a sponge gene therapy could effectively reduce miR\u2010146a activity and attenuate neointimal formation in vein grafts, suggesting its potential therapeutic application for prevention of vein graft failure. \u00a9 2018 IUBMB Life, 71(1):125\u2013133, 2019<\/jats:p>","DOI":"10.1002\/iub.1946","type":"journal-article","created":{"date-parts":[[2018,10,6]],"date-time":"2018-10-06T16:25:18Z","timestamp":1538843118000},"page":"125-133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MicroRNA\u2010146a sponge therapy suppresses neointimal formation in rat vein grafts"],"prefix":"10.1002","volume":"71","author":[{"given":"Bo\u2010Jun","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Shanghai Sixth People's Hospital Shanghai Jiao Tong University  Shanghai 200233 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