Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk.
Arterioscler Thromb Vasc Biol
; 33(11): 2666-73, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23968978
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Proteína C-Reativa
/
Doenças Cardiovasculares
/
Interleucina-6
/
Obesidade
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
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Humans
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Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article