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dc.contributor.authorGranata, Alessandra
dc.contributor.authorKasioulis, Ioannis
dc.contributor.authorSerrano, Felipe
dc.contributor.authorCooper, James D
dc.contributor.authorTraylor, Matthew
dc.contributor.authorSinha, Sanjay
dc.contributor.authorMarkus, Hugh S
dc.date.accessioned2022-04-13T08:00:50Z
dc.date.available2022-04-13T08:00:50Z
dc.date.issued2022
dc.date.submitted2022-01-06
dc.identifier.issn2297-055X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336048
dc.description.abstractA common variant in the Histone Deacetylase 9 (HDAC9) gene is the strongest genetic risk for large-vessel stroke, and HDAC9 offers a novel target for therapeutic modulation. However, the mechanisms linking the HDAC9 variant with increased stroke risk is still unclear due to the lack of relevant models to study the underlying molecular mechanisms. We generated vascular smooth muscle cells using human induced pluripotent stem cells with the HDAC9 stroke risk variant to assess HDAC9-mediated phenotypic changes in a relevant cells model and test the efficacy of HDAC inhibitors for potential therapeutic strategies. Our human induced pluripotent stem cells derived vascular smooth muscle cells show enhanced HDAC9 expression and allow us to assess HDAC9-mediated effects on promoting smooth muscle cell dysfunction, including proliferation, migration, apoptosis and response to inflammation. These phenotypes could be reverted by treatment with HDAC inhibitors, including sodium valproate and small molecules inhibitors. By demonstrating the relevance of the model and the efficacy of HDAC inhibitors, our model provides a robust phenotypic screening platform, which could be applied to other stroke-associated genetic variants.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectCardiovascular Medicine
dc.subjectHDAC9
dc.subjecthuman induced pluripotent stem (hiPS) cells
dc.subjectischemic stroke
dc.subjectsmooth muscle cells
dc.subjectrisk variant
dc.titleThe Histone Deacetylase 9 Stroke-Risk Variant Promotes Apoptosis and Inflammation in a Human iPSC-Derived Smooth Muscle Cells Model.
dc.typeArticle
dc.date.updated2022-04-13T08:00:49Z
prism.publicationNameFront Cardiovasc Med
prism.volume9
dc.identifier.doi10.17863/CAM.83477
dcterms.dateAccepted2022-03-04
rioxxterms.versionofrecord10.3389/fcvm.2022.849664
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSinha, Sanjay [0000-0001-5900-1209]
dc.contributor.orcidMarkus, Hugh [0000-0002-9794-5996]
dc.identifier.eissn2297-055X
pubs.funder-project-idBritish Heart Foundation (RG/17/5/32936)
pubs.funder-project-idBritish Heart Foundation (FS/18/46/33663)
pubs.funder-project-idNational Institute for Health Research (IS-BRC-1215-20014)
cam.issuedOnline2022-03-30


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