title: NLRP3 Inflammasome Expression and Activation in Human Atherosclerosis.
abstract: The NLR family, pyrin domain containing 3 (NLRP3) inflammasome is an interleukin (IL)-1β and IL-18 cytokine processing complex that is activated in inflammatory conditions. The role of the NLRP3 inflammasome in the pathogenesis of atherosclerosis and myocardial infarction is not fully understood.
  
  
  
  Atherosclerotic plaques were analyzed for transcripts of the NLRP3 inflammasome, and for IL-1β release. The Swedish First-ever myocardial Infarction study in Ac-county (FIA) cohort consisting of DNA from 555 myocardial infarction patients and 1016 healthy individuals was used to determine the frequency of 4 single nucleotide polymorphisms (SNPs) from the downstream regulatory region of NLRP3. Expression of NLRP3, Apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 (CASP1), IL1B, and IL18 mRNA was significantly increased in atherosclerotic plaques compared to normal arteries. The expression of NLRP3 mRNA was significantly higher in plaques of symptomatic patients when compared to asymptomatic ones. CD68-positive macrophages were observed in the same areas of atherosclerotic lesions as NLRP3 and ASC expression. Occasionally, expression of NLRP3 and ASC was also present in smooth muscle cells. Cholesterol crystals and ATP induced IL-1β release from lipopolysaccharide-primed human atherosclerotic lesion plaques. The minor alleles of the variants rs4266924, rs6672995, and rs10733113 were associated with NLRP3 mRNA levels in peripheral blood mononuclear cells but not with the risk of myocardial infarction.
  
  
  
  Our results indicate a possible role of the NLRP3 inflammasome and its genetic variants in the pathogenesis of atherosclerosis.
authors.affiliation: Cardiovascular Research Centre, Faculty of Medicine and Health, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Geena
authors.initials: G
authors.lastname: Paramel Varghese
authors.affiliation: Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.affiliation: Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rona J
authors.initials: RJ
authors.lastname: Strawbridge
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway K.G. Jebsen Inflammatory Research Center, University of Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Trine
authors.initials: T
authors.lastname: Ranheim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Krohg-Sørensen
authors.affiliation: Department of Neurology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Mona
authors.initials: M
authors.lastname: Skjelland
authors.affiliation: Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway K.G. Jebsen Inflammatory Research Center, University of Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mariette
authors.initials: M
authors.lastname: Lengquist
authors.affiliation: Department of Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hedin
authors.affiliation: Department of Internal Medicine, Skellefteå Hospital and Umeå University Hospital, Umeå, Sweden.
authors.forename: Jan-Håkan
authors.initials: JH
authors.lastname: Jansson
authors.affiliation: Cardiovascular Research Centre, Faculty of Medicine and Health, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Fransén
authors.affiliation: Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
authors.affiliation: Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.affiliation: Cardiovascular Research Centre, Faculty of Medicine and Health, School of Health and Medical Sciences, Örebro University, Örebro, Sweden allan.sirsjo@oru.se.
authors.forename: Allan
authors.initials: A
authors.lastname: Sirsjö
mesh_terms: D050197:Atherosclerosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D020170:Caspase 1 / Q000235:genetics; D018932:Chemokine CCL2 / Q000276:immunology; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics* / Q000276:immunology; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism*; D013548:Sweden; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D053468:CARD Signaling Adaptor Proteins; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508585:IL1B protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; D012333:RNA, Messenger; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D020170:Caspase 1
keywords: NLRP3; inflammasome; interleukin‐1β; myocardial infarction; polymorphism