Show simple item record

dc.contributor.authorYin 殷晓科, Xiaokeen
dc.contributor.authorWanga, Shaynahen
dc.contributor.authorFellows, Adam Len
dc.contributor.authorBarallobre-Barreiro, Javieren
dc.contributor.authorLu, Ruifangen
dc.contributor.authorDavaapil, Hongorzulen
dc.contributor.authorFranken, Romyen
dc.contributor.authorFava, Marikaen
dc.contributor.authorBaig, Ferheenen
dc.contributor.authorSkroblin, Philippen
dc.contributor.authorXing, Qiuruen
dc.contributor.authorKoolbergen, David Ren
dc.contributor.authorGroenink, Maartenen
dc.contributor.authorZwinderman, Aeilko Hen
dc.contributor.authorBalm, Ronen
dc.contributor.authorde Vries, Carlie JMen
dc.contributor.authorMulder, Barbara JMen
dc.contributor.authorViner, Rosaen
dc.contributor.authorJahangiri, Marjanen
dc.contributor.authorReinhardt, Dieter Pen
dc.contributor.authorSinha, Sanjayen
dc.contributor.authorde Waard, Vivianen
dc.contributor.authorMayr, Manuelen
dc.date.accessioned2019-07-25T23:31:18Z
dc.date.available2019-07-25T23:31:18Z
dc.date.issued2019-09en
dc.identifier.issn1079-5642
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/294949
dc.description.abstractOBJECTIVE: Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation. This study aimed to characterize the glycoproteome of the aortic ECM from patients with MFS and relate it to aortopathy. Approach and Results: ECM extracts of aneurysmal ascending aortic tissue from patients with and without MFS were enriched for glycopeptides. Direct N-glycopeptide analysis by mass spectrometry identified 141 glycoforms from 47 glycosites within 35 glycoproteins in the human aortic ECM. Notably, MFAP4 (microfibril-associated glycoprotein 4) showed increased and more diverse N-glycosylation in patients with MFS compared with control patients. MFAP4 mRNA levels were markedly higher in MFS aortic tissue. MFAP4 protein levels were also increased at the predilection (convexity) site for ascending aorta aneurysm in bicuspid aortic valve patients, preceding aortic dilatation. In human aortic smooth muscle cells, MFAP4 mRNA expression was induced by TGF (transforming growth factor)-β1 whereas siRNA knockdown of MFAP4 decreased FBN1 but increased elastin expression. These ECM changes were accompanied by differential gene expression and protein abundance of proteases from ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family and their proteoglycan substrates, respectively. Finally, high plasma MFAP4 concentrations in patients with MFS were associated with a lower thoracic descending aorta distensibility and greater incidence of type B aortic dissection during 68 months follow-up. CONCLUSIONS: Our glycoproteomics analysis revealed that MFAP4 glycosylation is enhanced, as well as its expression during the advanced, aneurysmal stages of MFS compared with control aneurysms from patients without MFS.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherLippincott Williams & Wilkins Ltd.
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAortaen
dc.subjectExtracellular Matrixen
dc.subjectMyocytes, Smooth Muscleen
dc.subjectHumansen
dc.subjectMarfan Syndromeen
dc.subjectAortic Aneurysm, Thoracicen
dc.subjectGlycopeptidesen
dc.subjectGlycoproteinsen
dc.subjectCarrier Proteinsen
dc.subjectExtracellular Matrix Proteinsen
dc.subjectProteomicsen
dc.subjectGlycosylationen
dc.subjectVascular Remodelingen
dc.subjectFibrillin-1en
dc.titleGlycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.en
dc.typeArticle
prism.endingPage1873
prism.issueIdentifier9en
prism.publicationDate2019en
prism.publicationNameArteriosclerosis, thrombosis, and vascular biologyen
prism.startingPage1859
prism.volume39en
dc.identifier.doi10.17863/CAM.42036
dcterms.dateAccepted2019-06-20en
rioxxterms.versionofrecord10.1161/atvbaha.118.312175en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-09en
dc.contributor.orcidBarallobre-Barreiro, Javier [0000-0001-6236-2304]
dc.contributor.orcidSinha, Sanjay [0000-0001-5900-1209]
dc.contributor.orcidMayr, Manuel [0000-0002-0597-829X]
dc.identifier.eissn1524-4636
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBritish Heart Foundation (RG/17/5/32936)
pubs.funder-project-idMRC (MC_PC_12009)


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

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