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dc.contributor.authorAalders, Jeffrey
dc.contributor.authorLéger, Laurens
dc.contributor.authorVan der Meeren, Louis
dc.contributor.authorVan den Vreken, Natasja
dc.contributor.authorSkirtach, Andre G
dc.contributor.authorSinha, Sanjay
dc.contributor.authorDe Backer, Julie
dc.contributor.authorvan Hengel, Jolanda
dc.date.accessioned2020-10-14T23:31:39Z
dc.date.available2020-10-14T23:31:39Z
dc.date.issued2020-10-07
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/311533
dc.description.abstractMarfan syndrome (MFS) is a systemic disorder of connective tissue caused by pathogenic variants in the fibrillin-1 (FBN1) gene. Myocardial dysfunction has been demonstrated in MFS patients and mouse models, but little is known about the intrinsic effect on the cardiomyocytes (CMs). In this study, both induced pluripotent stem cells derived from a MFS-patient and the line with the corrected FBN1 mutation were differentiated to CMs. Several functional analyses are performed on this model to study MFS related cardiomyopathy. Atomic force microscopy revealed that MFS CMs are stiffer compared to corrected CMs. The contraction amplitude of MFS CMs is decreased compared to corrected CMs. Under normal culture conditions, MFS CMs show a lower beat-to-beat variability compared to corrected CMs using multi electrode array. Isoproterenol-induced stress or cyclic strain demonstrates lack of support from the matrix in MFS CMs. This study reports the first cardiac cell culture model for MFS, revealing abnormalities in the behavior of MFS CMs that are related to matrix defects. Based on these results, we postulate that impaired support from the extracellular environment plays a key role in the improper functioning of CMs in MFS.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectMyocytes, Cardiac
dc.subjectHumans
dc.subjectMarfan Syndrome
dc.subjectCell Differentiation
dc.subjectMutation
dc.subjectAdult
dc.subjectInduced Pluripotent Stem Cells
dc.subjectFibrillins
dc.titleEffects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2020
prism.publicationNameSci Rep
prism.startingPage16756
prism.volume10
dc.identifier.doi10.17863/CAM.58626
dcterms.dateAccepted2020-09-21
rioxxterms.versionofrecord10.1038/s41598-020-73802-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-10-07
dc.contributor.orcidvan Hengel, Jolanda [0000-0003-0645-0435]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_PC_12009)
pubs.funder-project-idBritish Heart Foundation (RG/17/5/32936)
pubs.funder-project-idBritish Heart Foundation (FS/18/46/33663)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
cam.issuedOnline2020-10-07


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