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Thromb Haemost ; 118(12): 2112-2125, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30453346

ABSTRACT

BACKGROUND: Inflammation and coagulation are key processes in cardiovascular diseases (CVDs). The Canakinumab Anti-inflammatory Thrombosis Outcome Study trial affirmed the importance of inflammation in CVD by showing that inhibition of the interleukin (IL)-1ß pathway prevents recurrent CVD. A bi-directional relationship exists between inflammation and coagulation, but the precise interaction of platelets and IL-1ß-mediated inflammation is incompletely understood. We aimed to determine the inter-relationship between platelets and inflammation-and especially IL-1ß-in a cohort of healthy volunteers. METHODS: We used data from the 500-Human Functional Genomics cohort, which consists of approximately 500 Caucasian, healthy individuals. We determined associations of plasma levels of IL-1ß and other inflammatory proteins with platelet number and reactivity, the association of platelet reactivity with ex vivo cytokine production as well as the impact of genetic variations through a genome-wide association study (GWAS). RESULTS: Platelets were associated with IL-1ß on different levels. First, platelet number was positively associated with plasma IL-1ß concentrations (p = 8.9 × 10-9) and inversely with concentrations of α-1-anti-trypsin (p = 1.04 × 10-18), which is a known antagonist of IL-1ß. Second, platelet degranulation capacity, as determined by agonist-induced P-selectin expression, was associated with ex vivo IL-1ß and IL-6 production. Third, several platelet single-nucleotide polymorphisms (SNPs) were associated with cytokine production and there was a significant platelet SNP enrichment in specific biological important pathways. Finally, platelet SNPs were enriched among SNPs earlier identified in GWAS studies in blood-related diseases and immune-mediated diseases. CONCLUSION: This comprehensive assessment of factors associated with platelet number and reactivity reinforces the important inter-relationship of platelets and IL-1ß-mediated inflammation.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Blood Platelets/physiology , Cardiovascular Diseases/immunology , Genotype , Inflammation/immunology , Interleukin-1beta/immunology , Adult , Antibodies, Monoclonal, Humanized , Blood Coagulation , Cardiovascular Diseases/genetics , Cells, Cultured , Cohort Studies , Female , Humans , Inflammation/genetics , Interleukin-1beta/blood , Male , Platelet Activation/drug effects , Platelet Count , Polymorphism, Single Nucleotide , Young Adult
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