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dc.contributor.authorNiyonzima, Nathalie
dc.contributor.authorBakke, Siril S.
dc.contributor.authorGregersen, Ida
dc.contributor.authorHolm, Sverre
dc.contributor.authorSandanger, Øystein
dc.contributor.authorOrrem, Hilde Lang
dc.contributor.authorSporsheim, Bjørnar
dc.contributor.authorRyan, Liv
dc.contributor.authorKong, Xiang Yi
dc.contributor.authorDahl, Tuva Børresdatter
dc.contributor.authorSkjelland, Mona
dc.contributor.authorSørensen, Kirsten
dc.contributor.authorRokstad, Anne Mari A.
dc.contributor.authorYndestad, Arne
dc.contributor.authorLatz, Eicke
dc.contributor.authorGullestad, Lars
dc.contributor.authorAndersen, Geir Øystein
dc.contributor.authorDamås, Jan Kristian
dc.contributor.authorAukrust, Pål
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorEspevik, Terje
dc.description.abstractBackground: During atherogenesis, cholesterol precipitates into cholesterol crystals (CC) in the vessel wall, which trigger plaque inflammation by activating the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. We investigated the relationship between CC, complement and NLRP3 in patients with cardiovascular disease. Methods: We analysed plasma, peripheral blood mononuclear cells (PBMC) and carotid plaques from patients with advanced atherosclerosis applying ELISAs, multiplex cytokine assay, qPCR, immunohistochemistry, and gene profiling. Findings: Transcripts of interleukin (IL)-1beta(b) and NLRP3 were increased and correlated in PBMC from patients with acute coronary syndrome (ACS). Priming of these cells with complement factor 5a (C5a) and tumour necrosis factor (TNF) before incubation with CC resulted in increased IL-1b protein when compared to healthy controls. As opposed to healthy controls, systemic complement was significantly increased in patients with stable angina pectoris or ACS. In carotid plaques, complement C1q and C5b-9 complex accumulated around CC-clefts, and complement receptors C5aR1, C5aR2 and C3aR1 were higher in carotid plaques compared to control arteries. Priming human carotid plaques with C5a followed by CC incubation resulted in pronounced release of IL-1b, IL-18 and IL-1a. Additionally, mRNA profiling demonstrated that C5a and TNF priming followed by CC incubation upregulated plaque expression of NLRP3 inflammasome components. Interpretation: We demonstrate that CC are important local- and systemic complement activators, and we reveal that the interaction between CC and complement could exert its effect by activating the NLRP3 inflammasome, thus promoting the progression of atherosclerosis.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleCholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosisen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.localcode© 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal