Possible role of the NLRP3 inflammasome in the development of human atherosclerosis and myocardial infarction. — ASN Events
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  3. Possible role of the NLRP3 inflammasome in the development of human atherosclerosis and myocardial infarction.

Possible role of the NLRP3 inflammasome in the development of human atherosclerosis and myocardial infarction. (#314)

Geena Paramel 1 , Lasse Folkersen 2 , Rona Strawbridge 2 , Pål Aukrust 3 , karin franzen 1 , Allan Sirsjö 1
  1. Orebro University, Department of health and Medical science, Orebro, SE, Sweden
  2. Department of Medicine and Center for Molecular Medicine, , Karolinska Institutet, , solna, Stockholm, , Sweden
  3. Research Institute of Internal Medicine,Department of Thoracic and Cardiovascular Surgery ,K.G. Jebsen Inflammatory Research Center, Institue of Clinical Medicine ,Section of Clinical Immunology and Infectious Diseases, University of Oslo, Oslo

Abstract

Objective- The NLRP3 inflammasome is an 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 (MI) is not fully understood.

Approach and Results- Atherosclerotic plaques were analyzed for transcripts of the NLRP3 inflammasome, and for IL-1β release. The Swedish FIA cohort consisting of DNA from 555 MI patients and 1016 healthy individuals was used to determine the frequency of 5 SNPs from the downstream regulatory region of NLRP3. Expression of NLRP3, ASC, 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. Cholesterol crystals and ATP induced IL-1β release from LPS-primed human atherosclerotic lesion plaques. The minor alleles of the variants rs4266924, rs6672995 and rs10733113 were associated with NLRP3 mRNA levels in PBMCs and plaques but not with the risk of MI.

 Conclusions- Our results indicate a possible role of the NLRP3 inflammasomeand its genetic variantsin the pathogenesis of atherosclerosis.