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dc.contributor.authorSeyres, Denis
dc.contributor.authorCabassi, Alessandra
dc.contributor.authorLambourne, John J
dc.contributor.authorBurden, Frances
dc.contributor.authorFarrow, Samantha
dc.contributor.authorMcKinney, Harriet
dc.contributor.authorBatista, Joana
dc.contributor.authorKempster, Carly
dc.contributor.authorPietzner, Maik
dc.contributor.authorSlingsby, Oliver
dc.contributor.authorCao, Thong Huy
dc.contributor.authorQuinn, Paulene A
dc.contributor.authorStefanucci, Luca
dc.contributor.authorSims, Matthew C
dc.contributor.authorRehnstrom, Karola
dc.contributor.authorAdams, Claire L
dc.contributor.authorFrary, Amy
dc.contributor.authorErgüener, Bekir
dc.contributor.authorKreuzhuber, Roman
dc.contributor.authorMocciaro, Gabriele
dc.contributor.authorD'Amore, Simona
dc.contributor.authorKoulman, Albert
dc.contributor.authorGrassi, Luigi
dc.contributor.authorGriffin, Julian L
dc.contributor.authorNg, Leong Loke
dc.contributor.authorPark, Adrian
dc.contributor.authorSavage, David B
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorBock, Christoph
dc.contributor.authorDownes, Kate
dc.contributor.authorWareham, Nicholas J
dc.contributor.authorAllison, Michael
dc.contributor.authorVacca, Michele
dc.contributor.authorKirk, Paul DW
dc.contributor.authorFrontini, Mattia
dc.date.accessioned2022-04-14T01:02:28Z
dc.date.available2022-04-14T01:02:28Z
dc.date.issued2022-03-12
dc.identifier.issn1868-7075
dc.identifier.other35279219
dc.identifier.otherPMC8917653
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336092
dc.descriptionFunder: The National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and NIHR Rare Disease Translational Research Collaboration
dc.descriptionFunder: NIHR Leicester Biomedical Research Centre and the John and Lucille Van Geest Foundation
dc.descriptionFunder: British Heart Foundation Cambridge Centre of Excellence
dc.descriptionFunder: NIHR Cambridge Biomedical Research Centre
dc.descriptionFunder: NHS Health Education England
dc.descriptionFunder: Isaac Newton fellowship
dc.description.abstractBACKGROUND: This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. METHODS/RESULTS: We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. CONCLUSIONS: We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not displaying the classic features.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1868-7083
dc.sourcenlmid: 101516977
dc.subjectLipids
dc.subjectMetabolites
dc.subjectObesity
dc.subjectClassification
dc.subjectEpigenetics
dc.subjectLipodystrophy
dc.subjectBariatric Surgery
dc.subjectCardiometabolic Syndrome
dc.subjectInnate Immune Cells
dc.subjectMulti-omics
dc.titleTranscriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.
dc.typeArticle
dc.date.updated2022-04-14T01:02:28Z
prism.issueIdentifier1
prism.publicationNameClin Epigenetics
prism.volume14
dc.identifier.doi10.17863/CAM.83521
dcterms.dateAccepted2022-02-25
rioxxterms.versionofrecord10.1186/s13148-022-01257-z
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSeyres, Denis [0000-0002-2066-6980]
dc.identifier.eissn1868-7083
pubs.funder-project-idMedical Research Council (MC_UU_12012/1)
pubs.funder-project-idWellcome Trust (107064/Z/15/Z)
pubs.funder-project-idMedical Research Council (MR/R002363/1)
cam.issuedOnline2022-03-12


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International