Laboratory of Atherothrombosis, Moscow State University of Medicine and Dentistry, 11/6 Yauzskaya Street, Moscow, Russia, 119027.
Department of Internal Medicine and Cardiology, Charité University of Medicine Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Sci Rep. 2020 Dec 3;10(1):21114. doi: 10.1038/s41598-020-78004-y.
A proinflammatory dysregulation of cytokine release is associated with various diseases, in particular with those of infectious etiology, as well as with cardiovascular diseases (CVD). We showed earlier that cytokines are released in two forms, soluble and in association with extracellular vesicles (EVs). Here, we investigated the patterns of expression and clustering of soluble and EV-associated cytokines in patients with ST-elevation myocardial infarction (STEMI). We collected plasma samples from 48 volunteers without CVD and 62 patients with STEMI, separated soluble and EV fractions, and analyzed them for 33 cytokines using a multiplexed bead-based assay. We identified soluble and EV-associated cytokines that are upregulated in STEMI and form correlative clusters. Several clustered soluble cytokines were expressed almost exclusively in patients with STEMI. EV-associated cytokines were largely not affected by STEMI, except for pro-inflammatory cytokines IL-6, IL-18, and MIG, as well as anti-inflammatory IL-2 that were upregulated in a correlated fashion. Our results demonstrated that soluble cytokines in patients with STEMI are upregulated in a coordinated fashion in contrast to the mainly unaffected system of EV-associated cytokines. Identification of cytokine clusters affected differently by STEMI now permits investigation of their differential contributions to this pathology.
细胞因子释放的促炎失调与各种疾病有关，特别是与感染病因以及心血管疾病（CVD）有关。我们之前表明，细胞因子以两种形式释放，即可溶性形式和与细胞外囊泡（EVs）相关的形式。在这里，我们研究了 ST 段抬高型心肌梗死（STEMI）患者中可溶性和 EV 相关细胞因子的表达和聚类模式。我们从 48 名无 CVD 的志愿者和 62 名 STEMI 患者中收集了血浆样本，分离了可溶性和 EV 部分，并使用基于多重珠的分析方法对 33 种细胞因子进行了分析。我们确定了在 STEMI 中上调并形成相关簇的可溶性和 EV 相关细胞因子。几种聚类的可溶性细胞因子几乎仅在 STEMI 患者中表达。EV 相关细胞因子在 STEMI 中基本不受影响，除了促炎细胞因子 IL-6、IL-18 和 MIG 以及呈相关性上调的抗炎细胞因子 IL-2 外。我们的结果表明，与主要不受 STEMI 影响的 EV 相关细胞因子系统相比，STEMI 患者的可溶性细胞因子以协调的方式上调。现在，鉴定受 STEMI 影响不同的细胞因子簇可以研究它们对这种病理的不同贡献。
