title: Reduced expression of NLRP3 and MEFV in human ischemic heart tissue.
abstract: The innate immune system and, in particular, activation of the multi-protein complex known as the inflammasome complex are involved in ischemic injury in myocardial cells. The nucleotide-binding leucine-rich repeat-containing pyrin receptor 3 (NLRP3) inflammasome has been linked to inflammation and NLRP3 is especially important for increased inflammation in atherosclerosis, which may lead to myocardial infarction. Here we investigated how inflammasome molecules are affected in human ischemic heart tissue. Surprisingly the important member of the inflammasome complex, NLRP3, displayed markedly decreased levels in human ischemic heart tissue compared with non ischemic control heart tissue. However, subsequent gene analysis revealed mutations in NLRP3 in human ischemic heart tissues but not in non-ischemic control tissue. Gene polymorphisms in the NLRP3 inflammasome have been shown to be associated with increased IL-1β and IL-18 production and severe inflammation. The autoinflammatory disorder familial Mediterranean fever (FMF) is associated with decreased expression of the Mediterranean fever gene (MEFV) and increased inflammation. We also observed reduced expression of MEFV in ischemic versus non-ischemic heart tissue. Further analyses showed a mutation in MEFV in human ischemic heart tissue but not in non-ischemic control tissue. Our data show that defects in the inflammasome and associated proteins may be involved in promoting ischemic heart disease.
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hermansson
authors.forename: Annika
authors.initials: A
authors.lastname: Lundqvist
authors.forename: Carina
authors.initials: C
authors.lastname: Wasslavik
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.forename: Anders
authors.initials: A
authors.lastname: Jeppsson
authors.forename: Lillemor Mattsson
authors.initials: LM
authors.lastname: Hultén
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D058847:Inflammasomes / Q000235:genetics*; D009154:Mutation; D017202:Myocardial Ischemia / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000071198:Pyrin; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; C000604192:MEFV protein, human; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D000071198:Pyrin; D012333:RNA, Messenger