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Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension

dc.rights.licenseopenen_US
dc.contributor.authorHONG, Jason
dc.contributor.authorMEDZIKOVIC, Lejla
dc.contributor.authorSUN, Wasila
dc.contributor.authorWONG, Brenda
dc.contributor.authorRUFFENACH, Gregoire
dc.contributor.authorRHODES, Christopher J
dc.contributor.authorBROWNSTEIN, Adam
dc.contributor.authorLIANG, Lloyd L
dc.contributor.authorARYAN, Laila
dc.contributor.authorLI, Min
dc.contributor.authorVADGAMA, Arjun
dc.contributor.authorKURT, Zeyneb
dc.contributor.authorSCHWANTES-AN, Tae-Hwi
dc.contributor.authorMICKLER, Elizabeth A
dc.contributor.authorGRAF, Stefan
dc.contributor.authorEYRIES, Melanie
dc.contributor.authorLUTZ, Katie A
dc.contributor.authorPAUCIULO, Michael W
dc.contributor.authorTREMBATH, Richard C
dc.contributor.authorPERROS, Frederic
dc.contributor.authorMONTANI, David
dc.contributor.authorMORRELL, Nicholas W
dc.contributor.authorSOUBRIER, Florent
dc.contributor.authorWILKINS, Martin R
dc.contributor.authorNICHOLS, William C
dc.contributor.authorALDRED, Micheala A
dc.contributor.authorDESAI, Ankit A
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorUMAR, Soban
dc.contributor.authorSAGGAR, Rajan
dc.contributor.authorCHANNICK, Richard
dc.contributor.authorTUDER, Rubin M
dc.contributor.authorGERACI, Mark W
dc.contributor.authorSTEARMAN, Robert S
dc.contributor.authorYANG, Xia
dc.contributor.authorEGHBALI, Mansoure
dc.date.accessioned2024-10-14T07:51:34Z
dc.date.available2024-10-14T07:51:34Z
dc.date.issued2024-08-21
dc.identifier.issn1524-4539en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/202462
dc.description.abstractEnBACKGROUND: Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare. METHODS: We leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics. RESULTS: We identified 2 potentially protective gene network modules associated with vascular cells, and we validated ASPN, coding for asporin, as a key hub gene that is upregulated as a compensatory response to counteract PAH. We found that asporin is upregulated in lungs and plasma of multiple independent PAH cohorts and correlates with reduced PAH severity. We show that asporin inhibits proliferation and transforming growth factor-β/phosphorylated SMAD2/3 signaling in pulmonary artery smooth muscle cells from PAH lungs. We demonstrate in Sugen-hypoxia rats that ASPN knockdown exacerbated PAH and recombinant asporin attenuated PAH. CONCLUSIONS: Our integrative systems biology approach to dissect the PAH lung transcriptome uncovered asporin as a novel protective target with therapeutic potential in PAH.
dc.language.isoENen_US
dc.subject.enGene Expression Profiling
dc.subject.enMultiomics
dc.subject.enPulmonary Arterial Hypertension
dc.title.enIntegrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension
dc.title.alternativeCirculationen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1161/circulationaha.124.069864en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed39167456en_US
bordeaux.journalCirculationen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04734513
hal.version1
hal.date.transferred2024-10-14T07:51:39Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Circulation&rft.date=2024-08-21&rft.eissn=1524-4539&rft.issn=1524-4539&rft.au=HONG,%20Jason&MEDZIKOVIC,%20Lejla&SUN,%20Wasila&WONG,%20Brenda&RUFFENACH,%20Gregoire&rft.genre=article


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