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Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2666-73. doi: 10.1161/ATVBAHA.112.301112. Epub 2013 Aug 22.

Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk.

Author information

1
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.

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.

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

PMID:
23968978
PMCID:
PMC4289138
DOI:
10.1161/ATVBAHA.112.301112
[Indexed for MEDLINE]
Free PMC Article
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