{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:21:15Z","timestamp":1792095675064,"version":"4.4.0"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,1,21]]},"abstract":"\n Background<\/jats:title>\n \n Heart attacks and stroke often result from occlusive thrombi following the rupture of vulnerable atherosclerotic plaques. Vascular smooth muscle cells (\n VSMC<\/jats:styled-content>\n s) play a pivotal role in plaque vulnerability because of their switch towards a proinflammatory\/macrophage\u2010like phenotype when in the context of atherosclerosis. The prometastatic transcription factor Slug\/Snail2 is a critical regulator of cell phenotypic transition. Here, we aimed to investigate the role of Slug in the transdifferentiation process of\n VSMC<\/jats:styled-content>\n s occurring during atherogenesis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n In rat and human primary aortic smooth muscle cells, Slug protein expression is strongly and rapidly increased by platelet\u2010derived growth factor\u2010BB (PDGF\u2010\n BB<\/jats:styled-content>\n ).\n PDGF<\/jats:styled-content>\n \u2010\n BB<\/jats:styled-content>\n increases Slug protein without affecting\n mRNA<\/jats:styled-content>\n levels indicating that this growth factor stabilizes Slug protein. Immunocytochemistry and subcellular fractionation experiments reveal that\n PDGF<\/jats:styled-content>\n \u2010\n BB<\/jats:styled-content>\n triggers a rapid accumulation of Slug in\n VSMC<\/jats:styled-content>\n nuclei. Using pharmacological tools, we show that the\n PDGF<\/jats:styled-content>\n \u2010\n BB<\/jats:styled-content>\n \u2013dependent mechanism of Slug stabilization in\n VSMC<\/jats:styled-content>\n s involves the extracellular signal\u2010regulated kinase 1\/2 pathway. Immunohistochemistry experiments on type V and type\n VI<\/jats:styled-content>\n atherosclerotic lesions of human carotids show smooth muscle\u2013specific myosin heavy chain\u2013\/Slug\u2010positive cells surrounding the prothrombotic lipid core. In\n VSMC<\/jats:styled-content>\n s, Slug si\n RNA<\/jats:styled-content>\n s inhibit prostaglandin E2 secretion and prevent the inhibition of cholesterol efflux gene expression mediated by\n PDGF<\/jats:styled-content>\n \u2010\n BB<\/jats:styled-content>\n , known to be involved in plaque vulnerability and\/or thrombogenicity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our results highlight, for the first time, a role of Slug in aortic smooth muscle cell transdifferentiation and enable us to consider Slug as an actor playing a role in the atherosclerotic plaque progression towards a life\u2010threatening phenotype. This also argues for common features between acute cardiovascular events and cancer.<\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.014276","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T10:02:14Z","timestamp":1579600934000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Slug, a Cancer\u2010Related Transcription Factor, is Involved in Vascular Smooth Muscle Cell Transdifferentiation Induced by Platelet\u2010Derived Growth Factor\u2010BB During Atherosclerosis"],"prefix":"10.1161","volume":"9","author":[{"given":"Nah\u00e9ma","family":"Ledard","sequence":"first","affiliation":[{"name":"Institut de Biologie Paris\u2010Seine (IBPS) Biological Adaptation and Ageing UMR 8256 Sorbonne Universit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandrine","family":"Liboz","sequence":"additional","affiliation":[{"name":"INSERM 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