PDF(Pubmed)
Abstract：
Atherosclerotic plaques are sites of chronic inflammation with diverse cell contents and complex immune signaling. Plaque progression and destabilization are driven by the infiltration of immune cells and the cytokines that mediate their interactions. Here, we attempted to compare the systemic cytokine profiles in the blood plasma of patients with atherosclerosis and the local cytokine production, using ex vivo plaque explants from the same patients. The developed method of 41-plex xMAP data normalization allowed us to differentiate twenty-two cytokines produced by the plaque that were not readily detectable in free circulation and six cytokines elevated in blood plasma that may have other sources than atherosclerotic plaque. To verify the xMAP data on the putative atherogenesis-driving chemokines MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), RANTES (CCL5), and fractalkine (CX3CL1), qPCR was performed. The MIP1A (CCL3), MIP1B (CCL4), FKN (CX3CL1), and MCP1 (CCL2) genes were expressed at high levels in the plaques, whereas RANTES (CCL5) was almost absent. The expression patterns of the chemokines were restricted to the plaque cell types: the MCP1 (CCL2) gene was predominantly expressed in endothelial cells and monocytes/macrophages, MIP1A (CCL3) in monocytes/macrophages, and MIP1B (CCL4) in monocytes/macrophages and T cells. RANTES (CCL5) was restricted to T cells, while FKN (CX3CL1) was not differentially expressed. Taken together, our data indicate a plaque-specific cytokine production profile that may be a useful tool in atherosclerosis studies.
摘要：
动脉粥样硬化斑块是具有不同细胞含量和复杂免疫信号的慢性炎症部位。斑块进展和不稳定是由免疫细胞和介导其相互作用的细胞因子的浸润驱动的。这里,我们试图比较动脉粥样硬化患者血浆中的全身细胞因子谱和局部细胞因子的产生，使用来自同一患者的离体斑块外植体。41-plexxMAP数据标准化的开发方法使我们能够区分由斑块产生的22种在自由循环中不易检测到的细胞因子和血浆中升高的6种细胞因子，这些细胞因子可能具有动脉粥样硬化斑块以外的其他来源。为了验证假定的动脉粥样硬化驱动趋化因子MCP-1（CCL2）的xMAP数据，MIP-1α(CCL3),MIP-1β(CCL4),RANTES(CCL5),和Fractalkine(CX3CL1)，进行qPCR。MIP1A(CCL3),MIP1B(CCL4),FKN(CX3CL1),和MCP1（CCL2）基因在斑块中高水平表达，而RANTES（CCL5）几乎不存在。趋化因子的表达模式仅限于斑块细胞类型：MCP1（CCL2）基因主要在内皮细胞和单核细胞/巨噬细胞中表达，单核细胞/巨噬细胞中的MIP1A（CCL3），单核细胞/巨噬细胞和T细胞中的MIP1B(CCL4)。RANTES（CCL5）仅限于T细胞，而FKN(CX3CL1)不差异表达。一起来看,我们的数据表明,斑块特异性细胞因子产生谱可能是动脉粥样硬化研究的有用工具.
