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. Epub 2013 Aug 22.


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.

Keywords: cardiovascular disease; inflammation; mRNA platelets.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Blood Platelets / immunology*
  • Body Weight
  • C-Reactive Protein / metabolism*
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / immunology
  • Cardiovascular Diseases* / metabolism
  • Female
  • Gene Expression / immunology
  • Humans
  • Immunologic Factors / blood
  • Interleukin-6 / blood*
  • Male
  • Massachusetts / epidemiology
  • Middle Aged
  • Obesity* / epidemiology
  • Obesity* / immunology
  • Obesity* / metabolism
  • RNA / blood
  • Risk Factors


  • IL6 protein, human
  • Immunologic Factors
  • Interleukin-6
  • RNA
  • C-Reactive Protein