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dc.contributor.authorLunde, Ngoc Dieu Nguyen
dc.contributor.authorGregersen, Ida
dc.contributor.authorUeland, Thor
dc.contributor.authorShetelig, Christian
dc.contributor.authorHolm, Sverre
dc.contributor.authorKong, Xiang Yi
dc.contributor.authorMichelsen, Annika
dc.contributor.authorOtterdal, Kari
dc.contributor.authorYndestad, Arne
dc.contributor.authorBroch, Kaspar
dc.contributor.authorGullestad, Lars
dc.contributor.authorNyman, Tuula Anneli
dc.contributor.authorBendz, Bjørn
dc.contributor.authorEritsland, Jan
dc.contributor.authorHoffmann, Pavel
dc.contributor.authorSkagen, Karolina Ryeng
dc.contributor.authorGonçalves, Isabel
dc.contributor.authorNilsson, Jan
dc.contributor.authorGrenegård, Magnus
dc.contributor.authorPoreba, Marcin
dc.contributor.authorDrag, Marcin
dc.contributor.authorSeljeflot, Ingebjørg
dc.contributor.authorSporsheim, Bjørnar
dc.contributor.authorEspevik, Terje
dc.contributor.authorSkjelland, Mona
dc.contributor.authorJohansen, Harald Thidemann
dc.contributor.authorSolberg, Rigmor
dc.contributor.authorAukrust, Pål
dc.contributor.authorBjörbacka, Harry
dc.contributor.authorAndersen, Geir Øystein
dc.contributor.authorHalvorsen, Bente
dc.date.accessioned2020-04-03T08:28:15Z
dc.date.available2020-04-03T08:28:15Z
dc.date.issued2019-12-14
dc.description.abstract<i>Background and aims</i> - We have previously found increased levels of the cysteine protease legumain in plasma and plaques from patients with carotid atherosclerosis. This study further investigated legumain during acute cardiovascular events.<p><p> <i>Methods</i> - Circulating levels of legumain from patients and legumain released from platelets were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting were used to study expression, while localization was visualized by immunohistochemistry.<p><p> <i>Results</i> - In the <i>SUMMIT Malmö</i> cohort (n = 339 with or without type 2 diabetes and/or cardiovascular disease [CVD], and 64 healthy controls), the levels of circulating legumain were associated with the presence of CVD in non-diabetics, with no relation to outcome. In symptomatic carotid plaques and in samples from both coronary and intracerebral thrombi obtained during acute cardiovascular events, legumain was co-localized with macrophages in the same regions as platelets. <i>In vitro</i>, legumain was shown to be present in and released from platelets upon activation. In addition, THP-1 macrophages exposed to releasate from activated platelets showed increased legumain expression. Interestingly, primary peripheral blood mononuclear cells stimulated with recombinant legumain promoted anti-inflammatory responses. Finally, in a STEMI population (<i>POSTEMI</i>; n = 272), patients had significantly higher circulating legumain before and immediately after percutaneous coronary intervention compared with healthy controls (n = 67), and high levels were associated with improved outcome.<p><p> <i>Conclusions</i> - Our data demonstrate for the first time that legumain is upregulated during acute cardiovascular events and is associated with improved outcome.en_US
dc.identifier.citationLunde NDN, Gregersen I, Ueland T, Shetelig C, Holm S, Kong XY, Michelsen A, Otterdal K, Yndestad A, Broch K, Gullestad L, Nyman TA, Bendz B, Eritsland J, Hoffmann P, Skagen KR, Gonçalves, Nilsson J, Grenegård, Poreba M, Drag M, Seljeflot I, Sporsheim B, Espevik T, Skjelland M, Johansen HT, Solberg R, Aukrust P, Björbacka, Andersen GØ, Halvorsen BE. Legumain is upregulated in acute cardiovascular events and associated with improved outcome – potentially related to anti-inflammatory effects on macrophages. Atherosclerosis. 2019:1-9en_US
dc.identifier.cristinIDFRIDAID 1761084
dc.identifier.doi10.1016/j.atherosclerosis.2019.12.008
dc.identifier.issn0021-9150
dc.identifier.issn1879-1484
dc.identifier.urihttps://hdl.handle.net/10037/17995
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalAtherosclerosis
dc.relation.projectIDHelse Sør-Øst RHF: 2018084en_US
dc.relation.projectIDNorges forskningsråd: 144139en_US
dc.relation.projectIDNorges forskningsråd: 223255en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/SFF/223255/Norway/Centre of Molecular Inflammation Research/CEMIR/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/?/144139/Norway/?/?/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleLegumain is upregulated in acute cardiovascular events and associated with improved outcome – potentially related to anti-inflammatory effects on macrophagesen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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