Inflammation is a key factor in the development of atherosclerotic coronary artery disease. It is promoted through the inflammasome, a molecular machine that produces IL (interleukin)-1β in response to cholesterol crystal accumulation in macrophages. The CARD8 (caspase recruitment domain 8) protein modulates this process by suppressing caspase 1 and the transcription factor NF-κB (nuclear factor κB). The expression of CARD8 mRNA was examined in atherosclerotic vascular tissue and the impact on MI (myocardial infarction) of a polymorphism in the CARD8 gene determined. CARD8 mRNA was analysed by microarray of human atherosclerotic tissue and compared with transplant donor arterial tissue. Microarray analysis was performed for proximal genes associated with the rs2043211 locus in plaque. The CARD8 rs2043211 polymorphism was analysed by genotyping of two Swedish MI cohorts, FIA (First Myocardial Infarction in Northern Sweden) and SCARF (Stockholm Coronary Atherosclerosis Risk Factor). The CRP (C-reactive protein) level was measured in both cohorts, but the levels of the pro-inflammatory cytokines IL-1β, IL-18, TNF (tumour necrosis factor) and MCP-1 (monocyte chemoattractant protein) were measured in sera available from the SCARF cohort. CARD8 mRNA was highly expressed in atherosclerotic plaques compared with the expression in transplant donor vessel (P<0.00001). The minor allele was associated with lower expression of CARD8 in the plaques, suggesting that CARD8 may promote inflammation. Carriers of the minor allele of the rs2043211 polymorphism also displayed lower circulating CRP and lower levels of the pro-atherosclerotic chemokine MCP-1. However, no significant association could be detected between this polymorphism and MI in the two cohorts. Genetic alterations in the CARD8 gene therefore seem to be of limited importance for the development of MI.
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Research Article|
June 14 2013
CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation
Geena Varghese Paramel;
Geena Varghese Paramel
*Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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Lasse Folkersen;
Lasse Folkersen
†Atherosclerosis Research Unit, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
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Rona J. Strawbridge;
Rona J. Strawbridge
†Atherosclerosis Research Unit, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
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Ali Ateia Elmabsout;
Ali Ateia Elmabsout
*Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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Eva Särndahl;
Eva Särndahl
*Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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Pia Lundman;
Pia Lundman
‡Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden
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Jan-Håkan Jansson;
Jan-Håkan Jansson
§Department of Internal Medicine, Skellefteå Hospital and Umeå University Hospital, Umeå, Sweden
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Göran K. Hansson;
Göran K. Hansson
∥Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine at Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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Allan Sirsjö;
*Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden
Correspondence: Professor Allan Sirsjö (email allan.sirsjo@oru.se).
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Karin Fransén
Karin Fransén
*Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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Publisher: Portland Press Ltd
Received:
November 05 2012
Revision Received:
April 04 2013
Accepted:
April 23 2013
Accepted Manuscript online:
April 23 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 125 (8): 401–407.
Article history
Received:
November 05 2012
Revision Received:
April 04 2013
Accepted:
April 23 2013
Accepted Manuscript online:
April 23 2013
Citation
Geena Varghese Paramel, Lasse Folkersen, Rona J. Strawbridge, Ali Ateia Elmabsout, Eva Särndahl, Pia Lundman, Jan-Håkan Jansson, Göran K. Hansson, Allan Sirsjö, Karin Fransén; CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation. Clin Sci (Lond) 1 October 2013; 125 (8): 401–407. doi: https://doi.org/10.1042/CS20120572
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