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HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype

dc.rights.licenseopenen_US
dc.contributor.authorMALHOTRA, R.
dc.contributor.authorMAUER, A. C.
dc.contributor.authorLINO CARDENAS, C. L.
dc.contributor.authorGUO, X.
dc.contributor.authorYAO, J.
dc.contributor.authorZHANG, X.
dc.contributor.authorWUNDERER, F.
dc.contributor.authorSMITH, A. V.
dc.contributor.authorWONG, Q.
dc.contributor.authorPECHLIVANIS, S.
dc.contributor.authorHWANG, S. J.
dc.contributor.authorWANG, J.
dc.contributor.authorLU, Li
dc.contributor.authorNICHOLSON, C. J.
dc.contributor.authorSHELTON, G.
dc.contributor.authorBUSWELL, M. D.
dc.contributor.authorBARNES, H. J.
dc.contributor.authorSIGURSLID, H. H.
dc.contributor.authorSLOCUM, C.
dc.contributor.authorROURKE, C. O.
dc.contributor.authorRHEE, D. K.
dc.contributor.authorBAGCHI, A.
dc.contributor.authorNIGWEKAR, S. U.
dc.contributor.authorBUYS, E. S.
dc.contributor.authorCAMPBELL, C. Y.
dc.contributor.authorHARRIS, T.
dc.contributor.authorBUDOFF, M.
dc.contributor.authorCRIQUI, M. H.
dc.contributor.authorROTTER, J. I.
dc.contributor.authorJOHNSON, A. D.
dc.contributor.authorSONG, C.
dc.contributor.authorFRANCESCHINI, N.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorHOFFMANN, U.
dc.contributor.authorKALSCH, H.
dc.contributor.authorNOTHEN, M. M.
dc.contributor.authorSIGURDSSON, S.
dc.contributor.authorFREEDMAN, B. I.
dc.contributor.authorBOWDEN, D. W.
dc.contributor.authorJOCKEL, K. H.
dc.contributor.authorMOEBUS, S.
dc.contributor.authorERBEL, R.
dc.contributor.authorFEITOSA, M. F.
dc.contributor.authorGUDNASON, V.
dc.contributor.authorTHANASSOULIS, G.
dc.contributor.authorZAPOL, W. M.
dc.contributor.authorLINDSAY, M. E.
dc.contributor.authorBLOCH, D. B.
dc.contributor.authorPOST, W. S.
dc.contributor.authorO'DONNELL, C. J.
dc.date.accessioned2020-06-29T08:08:12Z
dc.date.available2020-06-29T08:08:12Z
dc.date.issued2019-11
dc.identifier.issn1546-1718 (Electronic) 1061-4036 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/8255
dc.description.abstractEnAortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 x 10(-8)). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.
dc.language.isoENen_US
dc.subject.enVINTAGE
dc.title.enHDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype
dc.title.alternativeNat Geneten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41588-019-0514-8en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed31659325en_US
bordeaux.journalNature Geneticsen_US
bordeaux.page1580-1587en_US
bordeaux.volume51en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03209858
hal.version1
hal.date.transferred2021-04-27T13:00:53Z
hal.exporttrue
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