Abstract

In this work, a comparative analysis of the myocardial cytokine profile was carried out in patients with coronary heart disease (CHD) and in patients with ischemic cardiomyopathy (ICM) against the background of CHD. The concentrations of 41 cytokines secreted by a 24-h tissue culture of the myocardium, intraoperatively collected from the right atrial (RA) appendage (control) and a peri-infarct zone (PZ) of the left ventricle (LV), were determined by the flow fluorimetry method using a multiplex test system. The aim of the work was to study in vitro the cytokine profile of myocardial cells to search for possible predictors of unfavorable outcomes of the surgical treatment of patients with CHD and ICM. The myocardial secretion of the pro-inflammatory molecules GM-CSF and IFN-γ increased significantly in patients with ICM against the background of CHD (up to 78–80 pg/g, p < 0.05) as compared with zero values in the case of CHD. At the same time, a threefold decrease in the concentration of the Fractalkine 3 ligand (Flt-3L, fms-like tyrosine kinase 3 ligand) was observed. A decrease in the secretion of Flt-3L was noted namely in the PZ–LV as compare with the RA appendage. In addition, the concentrations of fibroblast growth factor-2 (FGF-2), platelet-derived growth factor AB/BB (PDGF-AB/BB), interleukins IL-15 and IL-4, as well as regulated upon activation, normal T cell expressed and secreted (RANTES/CCL5), sharply decreased in the tissue myocardial PZ–LV culture as compared with RA appendage. The detected changes are analyzed using correlation and regression analyses; possible predictors of the risk of surgical treatment of patients from two groups are suggested. Pro-inflammatory cytokines (IL-5, IL-6) and chemokines (Flt-3L, IL-8), as well as factors of angiogenesis (VEGF) and angiostasis (IP-10), are suggested to be considered as potential markers of unfavorable outcome of the surgical treatment of cardiovascular diseases.

中文翻译：

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冠心病和缺血性心肌病心肌细胞的细胞因子谱

摘要

在这项工作中，对冠心病（CHD）患者和以冠心病为背景的缺血性心肌病（ICM）患者的心肌细胞因子谱进行了比较分析。术中从右心耳 (RA) 心耳 (对照) 和左心室 (LV) 梗死周围区 (PZ) 收集的 24 小时心肌组织培养物分泌的 41 种细胞因子的浓度通过以下方法测定使用多重测试系统的流式荧光测定法。这项工作的目的是在体外研究心肌细胞的细胞因子谱，以寻找 CHD 和 ICM 患者手术治疗不良结果的可能预测因素。与 CHD 背景下的 ICM 患者相比，促炎分子 GM-CSF 和 IFN-γ 的心肌分泌显着增加（高达 78-80 pg/g，p < 0.05），而 ICM 患者的心肌分泌量为零。冠心病。同时，观察到 Fractalkine 3 配体（Flt-3L，fms 样酪氨酸激酶 3 配体）的浓度降低了三倍。与 RA 附件相比，PZ-LV 中 Flt-3L 的分泌减少。此外，成纤维细胞生长因子-2 (FGF-2)、血小板源性生长因子 AB/BB (PDGF-AB/BB)、白细胞介素 IL-15 和 IL-4 的浓度以及激活后的调节，正常与 RA 附件相比，PZ-LV 组织心肌培养中 T 细胞表达和分泌 (RANTES/CCL5) 急剧下降。使用相关性和回归分析来分析检测到的变化；提出了两组患者手术治疗风险的可能预测因素。建议将促炎细胞因子（IL-5、IL-6）和趋化因子（Flt-3L、IL-8）以及血管生成因子（VEGF）和血管抑制因子（IP-10）视为潜在标志物心血管疾病手术治疗的不良结果。