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.
DOI of Published Version
McManus DD, Beaulieu LM, Mick E, Tanriverdi K, Larson MG, Keaney JF Jr, Benjamin EJ, Freedman JE. Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk. Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2666-73. doi: 10.1161/ATVBAHA.112.301112. Link to article on publisher's site
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.