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dc.contributor.authorMacGrogan, Donal 
dc.contributor.authorMartínez-Poveda, Beatriz
dc.contributor.authorDesvignes, Jean-Pierre
dc.contributor.authorFernandez-Friera, Leticia 
dc.contributor.authorGomez, Manuel J 
dc.contributor.authorGil Vilariño, Eduardo
dc.contributor.authorCallejas Alejano, Sergio
dc.contributor.authorGarcia-Pavia, Pablo 
dc.contributor.authorSolis, Jorge 
dc.contributor.authorLucena, Joaquín
dc.contributor.authorSalgado, David
dc.contributor.authorCollod-Béroud, Gwenaelle
dc.contributor.authorFaure, Emilie
dc.contributor.authorThéron, Alexis
dc.contributor.authorTorrents, Julia
dc.contributor.authorAvierinos, Jean-François
dc.contributor.authorMontes, Lorena
dc.contributor.authorDopazo, Ana 
dc.contributor.authorFuster, Valentin 
dc.contributor.authorIbanez, Borja 
dc.contributor.authorSanchez-Cabo, Fatima 
dc.contributor.authorZaffran, Stephane
dc.contributor.authorde la Pompa, Jose Luis 
dc.date.accessioned2021-04-22T06:17:34Z
dc.date.available2021-04-22T06:17:34Z
dc.date.issued2020-12-07
dc.identifier.citationPhysiol Genomics. 2020; 52(12):563-574es_ES
dc.identifier.issn1094-8341es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/12732
dc.description.abstractCalcific aortic valve disease (CAVD) is a significant cause of illness and death worldwide. Identification of early predictive markers could help optimize patient management. RNA-sequencing was carried out on human fetal aortic valves at gestational weeks 9, 13, and 22 and on a case-control study with adult noncalcified and calcified bicuspid and tricuspid aortic valves. In dimension reduction and clustering analyses, diseased valves tended to cluster with fetal valves at week 9 rather than normal adult valves, suggesting that part of the disease program might be due to reiterated developmental processes. The analysis of groups of coregulated genes revealed predominant immune-metabolic signatures, including innate and adaptive immune responses involving lymphocyte T-cell metabolic adaptation. Cytokine and chemokine signaling, cell migration, and proliferation were all increased in CAVD, whereas oxidative phosphorylation and protein translation were decreased. Discrete immune-metabolic gene signatures were present at fetal stages and increased in adult controls, suggesting that these processes intensify throughout life and heighten in disease. Cellular stress response and neurodegeneration gene signatures were aberrantly expressed in CAVD, pointing to a mechanistic link between chronic inflammation and biological aging. Comparison of the valve RNA-sequencing data set with a case-control study of whole blood transcriptomes from asymptomatic individuals with early aortic valve calcification identified a highly predictive gene signature of CAVD and of moderate aortic valve calcification in overtly healthy individuals. These data deepen and broaden our understanding of the molecular basis of CAVD and identify a peripheral blood gene signature for the early detection of aortic valve calcification.es_ES
dc.description.sponsorshipThis work was supported by the Ministerio de Ciencia, Innovacion y Universidades from Spain (MCIU) Grants SAF2016-78370-R, CB16/11/00399, CIBER CV, and RD16/0011/0021, TERCEL, Fundacion BBVA Grant BIO14_298, and Fundacion La Marato TV3 Grant 20153431 (to J.L.d.l.P.); and the Fondation Pour la Recherche Medicale Grant DPC20111123002 from l'Institut National de la Sante et de la Recherche Medicale and l'Association Francaise Contre les Myopathies Grant TRIM-RD) (to S.Z). The cost of this publication was supported in part with funds from the European Regional Development Fund. The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades (MCIU), the Instituto de Salud Carlos III (ISCIII), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (Grant SEV-2015-0505).es_ES
dc.language.isoenges_ES
dc.publisherAmerican Physiological Societyes_ES
dc.relation.isversionofPostprintes_ES
dc.subjectCAVDes_ES
dc.subjectgene signaturees_ES
dc.subjecthuman fetal valvees_ES
dc.subjectinflammationes_ES
dc.subjectperipheral blood biomarkeres_ES
dc.titleIdentification of a peripheral blood gene signature predicting aortic valve calcification.es_ES
dc.typeArtículoes_ES
dc.identifier.pubmedID33044885es_ES
dc.format.volume52es_ES
dc.format.number12es_ES
dc.format.page563-574es_ES
dc.identifier.doi10.1152/physiolgenomics.00034.2020es_ES
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1531-2267es_ES
dc.relation.publisherversionhttps://doi.org/10.1152/physiolgenomics.00034.2020es_ES
dc.identifier.journalPhysiological genomicses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Señalización Intercelular durante el Desarrollo y la Enfermedad Cardiovasculares_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Bioinformáticaes_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Genómicaes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovasculares_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionaleses_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-78370-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CB16/11/00399es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/RD16/0011/0021es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/embargoedAccesses_ES


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