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dc.contributor.authorUeland, Thor
dc.contributor.authorAbraityte, Aurelija
dc.contributor.authorNorum, Hilde
dc.contributor.authorVarathalingam, Sharanga
dc.contributor.authorGullestad, Lars
dc.contributor.authorAukrust, Pål
dc.contributor.authorAndreassen, Arne K.
dc.date.accessioned2021-08-20T10:41:27Z
dc.date.available2021-08-20T10:41:27Z
dc.date.issued2021-04-08
dc.description.abstractBackground and objective - Dysregulated Wnt signalling has been implicated in pulmonary hypertension (PH). We hypothesized that plasma levels of secreted Wnt proteins would be increased in patients with precapillary PH, correlate with indices of vascular resistance and cardiac function and give information on long-term prognosis.<p> <p>Methods - We measured the Wnt ligand Wnt5a and secreted Wnt antagonists Dickkopf (DKK) DKK1, DKK3, secreted frizzled-related protein 3 (sFRP3), Wnt inhibitory factor-1 (WIF1) and sclerostin (SOST) in 106 patients with precapillary PH and 40 healthy controls. A second sample was obtained after a median of 4 months (n = 52). During a median of 90 months follow-up, 67 patients died.<p> <p>Results - Our main findings were (i) Precapillary PH is characterized by enhanced systemic Wnt activity as reflected by elevated plasma levels of Wnt5a and secreted antagonists irrespective of diagnostic subgroups. (ii) WIF1 and in particular Wnt5a correlated with pulmonary vascular resistance and cardiac dysfunction. (iii) High levels of Wnt5a, sFRP3, DKK3 and WIF1 were associated with poor prognosis in age- and sex-adjusted analysis (hazard ratios per log/SD change ~1.4) and for DKK3 after further adjustment with right arterial pressure, pulmonary oxygen saturation, cardiac index, N-terminal pro B-type natriuretic peptide and peak oxygen uptake (VO2). Finally, an elevation of Wnt5a and DKK3 during follow-up was independently associated with poor prognosis.<p> <p>Conclusion - Our data indicate that Wnt signalling pathways could be implicated in the pathogenesis of precapillary PH, and that some of the Wnt-related molecules (i.e., Wnt5a and DKK3) should be further investigated in these patients.en_US
dc.identifier.citationUeland, Abraityte, Norum, Varathalingam, Gullestad, Aukrust, Andreassen. Circulating regulators of the wingless pathway in precapillary pulmonary hypertension. Respirology (Carlton South. Print). 2021;26(6):574-581en_US
dc.identifier.cristinIDFRIDAID 1926898
dc.identifier.doi10.1111/resp.14048
dc.identifier.issn1323-7799
dc.identifier.issn1440-1843
dc.identifier.urihttps://hdl.handle.net/10037/22192
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.journalRespirology (Carlton South. Print)
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_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 regulators of the wingless pathway in precapillary pulmonary hypertensionen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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