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dc.contributor.authorNorum, Hilde Margrethe
dc.contributor.authorMichelsen, Annika
dc.contributor.authorLekva, Tove
dc.contributor.authorArora, Satish
dc.contributor.authorOtterdal, Kari
dc.contributor.authorOlsen, Maria Belland
dc.contributor.authorKong, Xiang Yi
dc.contributor.authorGude, Einar
dc.contributor.authorAndreassen, Arne K.
dc.contributor.authorSolbu, Dag
dc.contributor.authorKarason, Kristjan
dc.contributor.authorDellgren, Göran
dc.contributor.authorGullestad, Lars
dc.contributor.authorAukrust, Pål
dc.contributor.authorUeland, Thor
dc.date.accessioned2019-04-12T11:52:48Z
dc.date.available2019-04-12T11:52:48Z
dc.date.issued2018-10-12
dc.description.abstractCardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta‐like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n = 70) randomized to standard or EVR‐based, calcineurin inhibitor‐free immunosuppression and in maintenance HTx recipients (n = 41). Compared to healthy controls, plasma DLL1 and POSTN were elevated in de novo (<i>P</i> < .01; <i>P</i> < .001) and maintenance HTx recipients (<i>P</i> < .001; <i>P</i> < .01). Use of EVR was associated with a treatment effect for DLL1. For de novo HTx recipients, a change in DLL1 correlated with a change in CAV at 1 (<i>P</i> = .021) and 3 years (<i>P</i> = .005). In vitro, activation of T cells increased DLL1 secretion, attenuated by EVR. In vitro data suggest that also endothelial cells and vascular smooth muscle cells (VSMCs) could contribute to circulating DLL1. Immunostaining of myocardial specimens showed colocalization of DLL1 with T cells, endothelial cells, and VSMCs. Our findings suggest a role of DLL1 in CAV progression, and that the beneficial effect of EVR on CAV could reflect a suppressive effect on DLL1.en_US
dc.description.sponsorshipRaagholt and Kardimmun Foundationsen_US
dc.descriptionThis is the pre-peer reviewed version of the following article: Norum, H.M., Michelsen, A.E., Lekva, T., Arora, S., Otterdal, K., Olsen, M.B. ... Ueland, T. (2018). Circulating delta‐like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus‐based immunosuppression. <i>American journal of transplantation, 19</i>(4), 1050-1060, which has been published in final form at <a href=https://doi.org/10.1111/ajt.15141>https://doi.org/10.1111/ajt.15141. </a> This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.en_US
dc.identifier.citationNorum, H.M., Michelsen, A.E., Lekva, T., Arora, S., Otterdal, K., Olsen, M.B. ... Ueland, T. (2018). Circulating delta‐like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus‐based immunosuppression. <i>American journal of transplantation, 19</i>(4), 1050-1060. https://doi.org/10.1111/ajt.15141en_US
dc.identifier.cristinIDFRIDAID 1641904
dc.identifier.doi10.1111/ajt.15141
dc.identifier.issn1600-6135
dc.identifier.issn1600-6143
dc.identifier.urihttps://hdl.handle.net/10037/15202
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.journalAmerican Journal of Transplantation
dc.rights.accessRightsopenAccessen_US
dc.subjectclinical research/practiceen_US
dc.subjecteverolimusen_US
dc.subjectheart transplantation/cardiologyen_US
dc.subjectimmunosuppressant ‐ mechanistic target of rapamycinen_US
dc.subjectimmunosuppression/immune modulationen_US
dc.subjectsignaling/signaling pathwaysen_US
dc.subjecttranslational research/scienceen_US
dc.subjectvasculopathyen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleCirculating delta-like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus-based immunosuppressionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US


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