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.
Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2666-73. doi: 10.1161/ATVBAHA.112.301112. Epub 2013 Aug 22.
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.
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.
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.
心血管疾病是一种复杂的疾病，受遗传变异与环境因素相互作用的影响。然而，目前尚无来自大型社区研究的信息来检验循环细胞特异性 RNA 与炎症蛋白之间的关系。鉴于炎症生物标志物、肥胖、血小板功能与心血管疾病之间的关联，我们试图研究 C 反应蛋白（CRP）和白细胞介素-6（IL-6）与血小板中关键炎症转录物表达的关系。
我们在弗雷明汉心脏研究（FHS）后代队列检查 8 中量化了 1625 名参与者的循环 CRP 和 IL-6 水平（平均年龄 66.6±6.6 岁；46%为男性）。我们通过高通量定量逆转录聚合酶链反应测量了源自血小板衍生 RNA 的 15 个相关基因的表达，并使用多元回归来关联 CRP 和 IL-6 血清浓度与基因表达。CRP 和 IL-6 水平与 15 个血小板衍生炎症转录物中的 10 个相关，包括 ALOX5、CRP、IFIT1、IL6、PTGER2、S100A9、SELENBP1、TLR2、TLR4 和 TNFRSF1B（P<0.001）。在对可能的混杂因素进行多变量调整后，CRP 和 IL-6 与血小板 mRNA 表达之间的关联仍然存在。在 FHS 样本中与 CRP 或 IL-6 呈正相关的 6 个基因在受到 CRP 或 IL-6 刺激时也在上皮细胞中上调。
我们的数据强调了循环炎症生物标志物 CRP 和 IL-6 与血小板基因表达之间的紧密联系，同时也考虑了心血管疾病的危险因素。我们的结果还表明，体重可能直接影响这些关联。
