{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:29:45Z","timestamp":1785932985168,"version":"3.56.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T00:00:00Z","timestamp":1396915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Greta and Johan Kocks Foundation"},{"DOI":"10.13039\/501100001862","name":"The Swedish Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001862","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Thureus Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The polyamines putrescine, spermidine and spermine play essential roles in cell proliferation and migration, two processes involved in the development of vascular disease. Thus, intervention with polyamine formation may represent a way to inhibit unwanted vascular smooth muscle cell (<jats:styled-content style=\"fixed-case\">VSMC<\/jats:styled-content>) proliferation. The aim of the present study was to assess the importance of polyamines for <jats:styled-content style=\"fixed-case\">VSMC<\/jats:styled-content> proliferation and vascular contractility. The rate\u2010limiting step in polyamine biosynthesis is catalysed by ornithine decarboxylase (<jats:styled-content style=\"fixed-case\">ODC<\/jats:styled-content>). Treatment with \u03b1\u2010difluoromethylornithine (<jats:styled-content style=\"fixed-case\">DFMO<\/jats:styled-content>), an irreversible inhibitor of <jats:styled-content style=\"fixed-case\">ODC<\/jats:styled-content>, reduced <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> synthesis in primary rat <jats:styled-content style=\"fixed-case\">VSMC<\/jats:styled-content>s in a concentration\u2010dependent manner with an <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> value of 100\u00a0\u03bcM. Moreover, <jats:styled-content style=\"fixed-case\">DFMO<\/jats:styled-content> reduced <jats:styled-content style=\"fixed-case\">VSMC<\/jats:styled-content> migration assessed in a scratch assay. The <jats:styled-content style=\"fixed-case\">DFMO<\/jats:styled-content>\u2010induced attenuation of <jats:styled-content style=\"fixed-case\">VSMC<\/jats:styled-content> proliferation was associated with lowered cellular amount of polyamines. The antiproliferative effect of <jats:styled-content style=\"fixed-case\">DFMO<\/jats:styled-content> was specific because supplementation with polyamines reversed the effect of <jats:styled-content style=\"fixed-case\">DFMO<\/jats:styled-content> on proliferation and normalized cellular polyamine levels. Isometric force recordings in cultured rat tail artery rings showed that <jats:styled-content style=\"fixed-case\">DFMO<\/jats:styled-content> counteracts the decrease in contractility caused by culture with foetal bovine serum as growth stimulant. We conclude that inhibition of polyamine synthesis by <jats:styled-content style=\"fixed-case\">DFMO<\/jats:styled-content> may limit the first wave of cell proliferation and migration, which occurs in the acute phase after vascular injury. Besides its antiproliferative effect, <jats:styled-content style=\"fixed-case\">DFMO<\/jats:styled-content> may prevent loss of the smooth muscle contractile phenotype in vascular injury.<\/jats:p>","DOI":"10.1111\/bcpt.12237","type":"journal-article","created":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T09:11:28Z","timestamp":1395738688000},"page":"379-388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of Polyamine Formation Antagonizes Vascular Smooth Muscle Cell Proliferation and Preserves the Contractile Phenotype"],"prefix":"10.1111","volume":"115","author":[{"given":"Mario","family":"Grossi","sequence":"first","affiliation":[{"name":"Department of Experimental Medical Science Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo","family":"Persson","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science Lund 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