The CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation

Inflammation is a key factor in the development of atherosclerotic coronary artery disease. It is promoted through the inflammasome, a molecular machine that produces interleukin-1β in response to cholesterol crystal accumulation in macrophages. The CARD8 protein modulates this process by suppressing caspase-1 and the transcription factor NF-κB. The expression of CARD8 mRNA was examined in atherosclerotic vascular tissue and the impact on myocardial infarction (MI) of a polymorphism in the CARD8 gene. CARD8 mRNA was analyzed by microarray of human atherosclerotic tissue and compared to transplant donor arterial tissue. Microarray analysis was performed for proximal genes associated with the rs2043211 locus in plaque. The CARD8 rs2043211 polymorphism was analyzed by genotyping of two Swedish MI cohorts, FIA and SCARF. The CRP level was measured in both cohorts, but the levels of the pro-inflammatory cytokines IL-1β, IL-18, TNF, and MCP-1 were measured in sera available from the SCARF cohort. CARD8 mRNA was highly expressed in atherosclerotic plaques compared to 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 be...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research