Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk
Department of Medicine, Division of Cardiovascular Medicine; Department of Quantitative Health Sciences; Meyers Primary Care Institute
Aged; Blood Platelets; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Female; Gene Expression; Humans; Immunologic Factors; Interleukin-6; Male; Massachusetts; Middle Aged; Obesity; RNA; Risk Factors
Cardiology | Cardiovascular Diseases | Epidemiology | Genetics and Genomics
OBJECTIVE: Cardiovascular disease is a complex disorder influenced by interactions of genetic variants with environmental factors. However, there is no information from large community-based studies examining the relationship of circulating cell-specific RNA to inflammatory proteins. In light of the associations among inflammatory biomarkers, obesity, platelet function, and cardiovascular disease, we sought to examine the relationships of C-reactive protein (CRP) and interleukin-6 (IL-6) to the expression of key inflammatory transcripts in platelets.
APPROACH AND RESULTS: We quantified circulating levels of CRP and IL-6 in 1625 participants of the Framingham Heart Study (FHS) Offspring cohort examination 8 (mean age, 66.6 ± 6.6 years; 46% men). We measured the expression of 15 relevant genes by high-throughput quantitative reverse transcriptase polymerase chain reaction from platelet-derived RNA and used multivariable regression to relate serum concentrations of CRP and IL-6 with gene expression. Levels of CRP and IL-6 were associated with 10 of the 15 platelet-derived inflammatory transcripts, ALOX5, CRP, IFIT1, IL6, PTGER2, S100A9, SELENBP1, TLR2, TLR4, and TNFRSF1B (P<0.001). Associations between platelet mRNA expression with CRP and IL-6 persisted after multivariable adjustment for potentially confounding factors. Six genes positively associated with CRP or IL-6 in the FHS sample were also upregulated in megakaryocytes in response to CRP or IL-6 exposure.
CONCLUSIONS: Our data highlight the strong connection between the circulating inflammatory biomarkers CRP and IL-6 and platelet gene expression, adjusting for cardiovascular disease risk factors. Our results also suggest that body weight may directly influence these associations.
Arteriosclerosis, thrombosis, and vascular biology
McManus, David D.; Beaulieu, Lea M.; Mick, Eric; Tanriverdi, Kahraman; Larson, Martin G.; Keaney, John F. Jr.; Benjamin, Emelia J.; and Freedman, Jane E., "Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk" (2013). University of Massachusetts Medical School Faculty Publications. 289.