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NLRP3 Inflammasome Expression and Activation in Human Atherosclerosis
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نویسنده
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paramel varghese g. ,folkersen l. ,strawbridge r.j. ,halvorsen b. ,yndestad a. ,ranheim t. ,krohg-sørensen k. ,skjelland m. ,espevik t. ,aukrust p. ,lengquist m. ,hedin u. ,jansson j.-h. ,fransén k. ,hansson g.k. ,eriksson p. ,sirsjö a.
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منبع
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journal of the american heart association - 2016 - دوره : 5 - شماره : 5
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چکیده
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Background: 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. methods and results: 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. conclusions: our results indicate a possible role of the nlrp3 inflammasome and its genetic variants in the pathogenesis of atherosclerosis. © 2016 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.
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کلیدواژه
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NLRP3; Inflammasome; Interleukin-1β; Myocardial infarction; Polymorphism
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آدرس
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cardiovascular research centre,faculty of medicine and health,school of health and medical sciences,örebro university,örebro, Sweden, department of medicine and center for molecular medicine,karolinska institutet,stockholm, Sweden, department of medicine and center for molecular medicine,karolinska institutet,stockholm, Sweden, research institute of internal medicine,oslo university hospital rikshospitalet,oslo,norway,institute of clinical medicine,university of oslo, Norway, research institute of internal medicine,oslo university hospital rikshospitalet,oslo,norway,k.g. jebsen inflammatory research center,university of oslo, Norway, research institute of internal medicine,oslo university hospital rikshospitalet,oslo,norway,institute of clinical medicine,university of oslo, Norway, department of thoracic and cardiovascular surgery,oslo university hospital rikshospitalet,oslo, Norway, department of neurology,oslo university hospital rikshospitalet,oslo, Norway, centre of molecular inflammation research,norwegian university of science and technology,trondheim, Norway, 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, department of surgery,karolinska university hospital,karolinska institutet,stockholm, Sweden, department of surgery,karolinska university hospital,karolinska institutet,stockholm, Sweden, department of internal medicine,skellefteå hospital and umeå university hospital,umeå, Sweden, cardiovascular research centre,faculty of medicine and health,school of health and medical sciences,örebro university,örebro, Sweden, department of medicine and center for molecular medicine,karolinska institutet,stockholm, Sweden, department of medicine and center for molecular medicine,karolinska institutet,stockholm, Sweden, cardiovascular research centre,faculty of medicine and health,school of health and medical sciences,örebro university,örebro, Sweden
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Authors
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