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Spontaneous PTB, resulting from preterm labor, is commonly caused by intrauterine infection\/ inflammation. Statins are well\u2010established, cholesterol\u2010lowering drugs that can reduce inflammation and inhibit vascular smooth muscle contraction. We show that simvastatin reduced the incidence of PTB in a validated intrauterine LPS\u2010induced PTB mouse model, decreased uterine proinflammatory mRNA concentrations (IL\u20106, Cxcl1, and Ccl2), and reduced serum IL\u20106 concentration. In human myometrial cells, simvastatin reduced proinflammatory mediator mRNA and protein expression (IL\u20106 and IL\u20108) and increased anti\u2010inflammatory cytokine mRNA expression (IL\u201010 and IL\u201013). Critically, simvastatin inhibited myometrial cell contraction, basally and during inflammation, and reduced phosphorylated myosin light chain concentration. Supplementation with mevalonate and geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, abolished these anticontractile effects, indicating that the Rho\/Rho\u2010associated protein kinase pathway is critically involved. Thus, simvastatin reduces PTB incidence in mice, inhibits myometrial contractions, and exhibits key anti\u2010inflammatory effects, providing a rationale for investigation into the repurposing of statins to treat preterm labor in women.\u2014Boyle, A. K., Rinaldi, S. F., Rossi, A. G., Saunders, P. T. K., Norman, J. E. Repurposing simvastatin as a therapy for preterm labor: evidence from preclinical models. FASEB J. 33, 2743\u20132758 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801104r","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T14:09:47Z","timestamp":1539353387000},"page":"2743-2758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Repurposing simvastatin as a therapy for preterm labor: evidence from preclinical models"],"prefix":"10.1096","volume":"33","author":[{"given":"Ashley K.","family":"Boyle","sequence":"first","affiliation":[{"name":"Tommy's Centre for Maternal and Fetal Health Medical Research Council (MRC) Centre for Reproductive Health University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara F.","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Tommy's Centre for Maternal and Fetal Health Medical Research Council (MRC) Centre for Reproductive Health University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano G.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Centre for Inflammation Research Queen's Medical Research Institute University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa T. 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