PMID- 23611467
OWN - NLM
STAT- MEDLINE
DCOM- 20130828
LR  - 20151119
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 125
IP  - 8
DP  - 2013 Oct
TI  - CARD8 gene encoding a protein of innate immunity is expressed in human 
      atherosclerosis and associated with markers of inflammation.
PG  - 401-7
LID - 10.1042/CS20120572 [doi]
AB  - 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)-1beta 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-kappaB (nuclear 
      factor kappaB). 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-1beta, 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.
FAU - Paramel, Geena Varghese
AU  - Paramel GV
AD  - Department of Clinical Medicine, School of Health and Medical Sciences, Orebro 
      University, Orebro, Sweden.
FAU - Folkersen, Lasse
AU  - Folkersen L
FAU - Strawbridge, Rona J
AU  - Strawbridge RJ
FAU - Elmabsout, Ali Ateia
AU  - Elmabsout AA
FAU - Sarndahl, Eva
AU  - Sarndahl E
FAU - Lundman, Pia
AU  - Lundman P
FAU - Jansson, Jan-Hakan
AU  - Jansson JH
FAU - Hansson, Goran K
AU  - Hansson GK
FAU - Sirsjo, Allan
AU  - Sirsjo A
FAU - Fransen, Karin
AU  - Fransen K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Biomarkers)
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (CARD8 protein, human)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Neoplasm Proteins)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Atherosclerosis/blood/*genetics
MH  - Biomarkers/blood
MH  - C-Reactive Protein/metabolism
MH  - CARD Signaling Adaptor Proteins/*genetics
MH  - Chemokine CCL2/blood
MH  - Cohort Studies
MH  - Cytokines/blood
MH  - *Gene Expression Profiling
MH  - Gene Frequency
MH  - Genotype
MH  - Humans
MH  - Immunity, Innate/genetics
MH  - Inflammation/blood/*genetics
MH  - Inflammation Mediators/blood
MH  - Myocardial Infarction/blood/genetics
MH  - Neoplasm Proteins/*genetics
MH  - Oligonucleotide Array Sequence Analysis
MH  - Plaque, Atherosclerotic/blood/genetics
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - Sweden
EDAT- 2013/04/25 06:00
MHDA- 2013/08/29 06:00
CRDT- 2013/04/25 06:00
PHST- 2013/04/25 06:00 [entrez]
PHST- 2013/04/25 06:00 [pubmed]
PHST- 2013/08/29 06:00 [medline]
AID - CS20120572 [pii]
AID - 10.1042/CS20120572 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2013 Oct;125(8):401-7. doi: 10.1042/CS20120572.