Proteomic analysis of descending thoracic aorta identifies unique and universal signatures of aneurysm and dissection

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dc.contributor.authorSaddic, Louisen
dc.contributor.authorOrosco, Amandaen
dc.contributor.authorGuo, Dongchuanen
dc.contributor.authorMilewicz, Dianna M.en
dc.contributor.authorTroxlair, Danaen
dc.contributor.authorVander Heide, Richarden
dc.contributor.authorHerrington, David M.en
dc.contributor.authorWang, Yueen
dc.contributor.authorAzizzadeh, Alien
dc.contributor.authorParker, Sarah J.en
dc.date.accessioned2023-01-24T14:34:13Zen
dc.date.available2023-01-24T14:34:13Zen
dc.date.issued2022en
dc.date.updated2023-01-24T02:48:53Zen
dc.description.abstractObjective: Very few clinical predictors of descending thoracic aorta dissection have been determined. Although aneurysms can dissect in a size-dependent process, most descending dissections will occur without prior enlargement. We compared the proteomic profiles of normal, dissected, aneurysm, and both aneurysm and dissected descending thoracic aortas to identify novel biomarkers and further understand the molecular pathways that lead to tissue at risk of dissection. Methods: We performed proteomic profiling of descending thoracic aortas with four phenotypes: normal (n = 46), aneurysm (n = 22), dissected (n = 12), and combined aneurysm and dissection (n = 8). Pairwise differential protein expression analyses using a Bayesian approach were then performed to identify common proteins that were dysregulated between each diseased tissue type and control aorta and to uncover unique proteins between aneurysmal and dissected aortas. Network and Markov cluster algorithms of differentially expressed proteins were used to find enriched ontology processes. A convex analysis of mixtures was also performed to identify the molecular subtypes within the different tissue types. Results: The diseased aortas had 71 common differentially expressed proteins compared with the control, including higher amounts of the protein thrombospondin 1. We found 42 differentially expressed proteins between the aneurysm and dissected tissue, with an abundance of apolipoproteins in the former and higher quantities of extracellular matrix proteins in the latter. The convex analysis of mixtures showed enhancement of a molecular subtype enriched in contractile proteins within the control tissue compared with the diseased tissue, in addition to increased proportions of molecular subtypes enriched in inflammation and red blood cell expression in the aneurysmal compared with the dissected tissue. Conclusions: We found some overlapping differentially expressed proteins in aneurysmal and nonaneurysmal descending thoracic aortas at risk of dissection compared with normal aortas. However, we also found uniquely altered molecular pathways that might uncover mechanisms for dissection.en
dc.description.versionPublished versionen
dc.format.extentPages 85-181en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.jvssci.2022.01.001en
dc.identifier.eissn2666-3503en
dc.identifier.issn2666-3503en
dc.identifier.orcidWang, Yue [0000-0002-1788-1102]en
dc.identifier.otherPMC8914561en
dc.identifier.otherS2666-3503(22)00001-3 (PII)en
dc.identifier.pmid35280433en
dc.identifier.urihttp://hdl.handle.net/10919/113389en
dc.identifier.volume3en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35280433en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectAneurysmen
dc.subjectDescending thoracic aortaen
dc.subjectDissectionen
dc.subjectProteomicsen
dc.subjectClinical Researchen
dc.subjectBiotechnologyen
dc.subjectCardiovascularen
dc.subject2 Aetiologyen
dc.subject2.1 Biological and endogenous factorsen
dc.titleProteomic analysis of descending thoracic aorta identifies unique and universal signatures of aneurysm and dissectionen
dc.title.serialJVS-Vascular Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2022-01-05en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/Engineering/Electrical and Computer Engineeringen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen

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