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Tamoxifen Accelerates Endothelial Healing by Targeting ERα in Smooth Muscle Cells.

dc.rights.licenseembargoen_US
dc.contributor.authorZAHREDDINE, Rana
dc.contributor.authorDAVEZAC, Morgane
dc.contributor.authorSMIRNOVA, Natalia
dc.contributor.authorBUSCATO, Melissa
dc.contributor.authorLHUILLIER, Emeline
dc.contributor.authorLUPIERI, Adrien
dc.contributor.authorSOLINHAC, Romain
dc.contributor.authorVINEL, Alexia
dc.contributor.authorVESSIERES, Emilie
dc.contributor.authorHENRION, Daniel
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorRENAULT, Marie-Ange
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGADEAU, Alain-Pierre
dc.contributor.authorFLOURIOT, Gilles
dc.contributor.authorLENFANT, Françoise
dc.contributor.authorLAFFARGUE, Muriel
dc.contributor.authorMÉTIVIER, Raphaël
dc.contributor.authorARNAL, Jean-François
dc.contributor.authorFONTAINE, Coralie
dc.date.accessioned2021-03-04T11:15:48Z
dc.date.available2021-03-04T11:15:48Z
dc.date.issued2020-12-04
dc.identifier.issn1524-4571en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26435
dc.description.abstractEnTamoxifen prevents the recurrence of breast cancer and is also beneficial against bone demineralization and arterial diseases. It acts as an ER (estrogen receptor) α antagonist in ER-positive breast cancers, whereas it mimics the protective action of 17β-estradiol in other tissues such as arteries. However, the mechanisms of these tissue-specific actions remain unclear. Here, we tested whether tamoxifen is able to accelerate endothelial healing and analyzed the underlying mechanisms. Using 3 complementary mouse models of carotid artery injury, we demonstrated that both tamoxifen and estradiol accelerated endothelial healing, but only tamoxifen required the presence of the underlying medial smooth muscle cells. Chronic treatment with 17β-estradiol and tamoxifen elicited differential gene expression profiles in the carotid artery. The use of transgenic mouse models targeting either whole ERα in a cell-specific manner or ERα subfunctions (membrane/extranuclear versus genomic/transcriptional) demonstrated that 17β-estradiol-induced acceleration of endothelial healing is mediated by membrane ERα in endothelial cells, while the effect of tamoxifen is mediated by the nuclear actions of ERα in smooth muscle cells. Whereas tamoxifen acts as an antiestrogen and ERα antagonist in breast cancer but also on the membrane ERα of endothelial cells, it accelerates endothelial healing through activation of nuclear ERα in smooth muscle cells, inviting to revisit the mechanisms of action of selective modulation of ERα.
dc.language.isoENen_US
dc.subject.enendothelium; estrogen; receptors
dc.subject.ensmooth muscle; tamoxifen; vascular
dc.title.enTamoxifen Accelerates Endothelial Healing by Targeting ERα in Smooth Muscle Cells.
dc.title.alternativeCirc Resen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1161/CIRCRESAHA.120.317062en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologie/Cardiologie et système cardiovasculaireen_US
dc.identifier.pubmed33012251en_US
bordeaux.journalCirculation Researchen_US
bordeaux.page1473-1487en_US
bordeaux.volume127en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue12en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.exportfalse
workflow.import.sourcepubmed
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Circulation%20Research&rft.date=2020-12-04&rft.volume=127&rft.issue=12&rft.spage=1473-1487&rft.epage=1473-1487&rft.eissn=1524-4571&rft.issn=1524-4571&rft.au=ZAHREDDINE,%20Rana&DAVEZAC,%20Morgane&SMIRNOVA,%20Natalia&BUSCATO,%20Melissa&LHUILLIER,%20Emeline&rft.genre=article


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