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

Area of Science:

• Cardiovascular biology
• Molecular medicine
• Inflammation research

Background:

• Cardiovascular disease (CVD) arises from complex genetic and environmental interactions.
• Inflammatory biomarkers, obesity, and platelet function are implicated in CVD.
• The relationship between cell-specific RNA and inflammatory proteins in community settings is understudied.

Purpose of the Study:

• To investigate the association between circulating C-reactive protein (CRP) and interleukin-6 (IL-6) levels and the expression of inflammatory gene transcripts in platelets.
• To explore these relationships in a large, community-based cohort.

Main Methods:

• Serum CRP and IL-6 levels were quantified in 1625 participants from the Framingham Heart Study Offspring cohort.
• Platelet-derived RNA was analyzed for the expression of 15 inflammatory genes using high-throughput quantitative reverse transcriptase polymerase chain reaction.
• Multivariable regression models were employed to assess the relationship between inflammatory protein levels and gene expression.

Main Results:

• CRP and IL-6 levels were significantly associated with the expression of 10 out of 15 investigated platelet inflammatory transcripts (P<0.001).
• These associations remained significant after adjusting for potential confounding factors.
• Six genes found to be associated with CRP or IL-6 in platelets were also upregulated in megakaryocytes upon exposure to these inflammatory mediators.

Conclusions:

• A robust link exists between circulating CRP and IL-6 and platelet gene expression, independent of common CVD risk factors.
• Body weight may play a direct role in modulating these observed associations.