title: Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk.
abstract: 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.
  
  
  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.
authors: From the National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (D.D.M., K.T., M.G.L., J.E.F.); Cardiology Division, Department of Medicine (D.D.M, L.M.B., K.T., J.F.K., J.E.F.) and Epidemiology Division, Department of Quantitative Health Sciences (D.D.M, E.M.), University of Massachusetts Medical School, Worcester, MA; Section of Cardiovascular Medicine, Department of Medicine (E.J.B.) and Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Preventive Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, MA (E.J.B.); and Department of Epidemiology (E.J.B.) and Department of Biostatistics (M.G.L.), Boston University School of Public Health, Boston, MA.
authors: David D
authors: DD
authors: McManus
authors: Lea M
authors: LM
authors: Beaulieu
authors: Eric
authors: E
authors: Mick
authors: Kahraman
authors: K
authors: Tanriverdi
authors: Martin G
authors: MG
authors: Larson
authors: John F
authors: JF
authors: Keaney
authors: Emelia J
authors: EJ
authors: Benjamin
authors: Jane E
authors: JE
authors: Freedman
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000276:immunology*; D001835:Body Weight; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D012313:RNA / Q000097:blood; D012307:Risk Factors
chemical_list: C508600:IL6 protein, human; D007155:Immunologic Factors; D015850:Interleukin-6; D012313:RNA; D002097:C-Reactive Protein
keywords: cardiovascular disease; inflammation; mRNA platelets
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