Abstract 14170: Circulating Interleukin-6 and C-Reactive Protein Levels are Related to Platelet Inflammatory Transcripts in the Framingham Heart Study
Background: Prior work has shown that inflammatory transcripts derived from platelets are associated with cardiovascular disease (CVD) risk factors and may play a role in the pathogenesis of heart disease. In light of the strong association between circulating inflammatory biomarkers and CVD, we sought to examine the relations of C-reactive protein (CRP) and Interleukin-6 (IL-6) and expression of 12 key inflammatory transcripts in platelets.
Methods: We quantified circulating levels of CRP and IL-6 in the Framingham laboratory using established methods from Framingham Offspring Examination 8 participants. On the basis of preliminary data and the prior literature, we measured expression of 12 genes by high-throughput quantitative reverse-transcriptase polymerase chain reaction in 1846 participants of the Framingham Offspring cohort from isolated platelet-derived RNA. We used multivariable regression to relate serum concentrations of CRP and IL-6 to quantitative platelet RNA expression.
Results: Levels of CRP were significantly associated with 10 specific platelet-derived transcripts, ALOX5, CD163, CRP, ICAM1, IFIT1, NFKB1, PTGER2, S100A9, SELENBP1, SIRPA, TLR2, TLR4, and TNFRSF1B (p<0.001), whereas IL-6 was associated with the same transcripts as well as IL6 and NFKBIA (p<0.001). Although inflammatory gene expression correlated with body mass index and Framingham Risk Score, associations between platelet-derived transcripts and CRP as well as IL-6 persisted after multivariate adjustment for these and other potentially confounding factors.
Conclusions: Platelet-derived inflammatory transcripts are associated with circulating levels of the inflammatory biomarkers CRP and IL-6. Although the cross-sectional nature of our analyses precludes causal inferences, our data highlight the strong connection between circulating levels of two biomarkers of prognostic importance in CVD and platelet inflammatory gene expression. Further data are needed to explore the connections between inflammation, platelet gene expression, and thrombosis in vivo.
- © 2012 by American Heart Association, Inc.