Heart failure (HF) is a complex clinical syndrome resulting from various cardiac diseases and a significant medical issue worldwide. Although the role of inflammation in HF pathogenesis is well-known, the specific cell types and regulatory molecules involved remain poorly understood. Here, we identified key cell types and novel biomarkers via an analysis of single-cell and bulk RNA sequencing data obtained from patients with two major HF types of ischemic cardiomyopathy and dilated cardiomyopathy. Myeloid cells were identified as the primary cell population involved in HF through cellular fraction and gene set enrichment analysis. Additionally, differential analysis of myeloid cells revealed crosstalk between cellular communication and cytokine-regulated immune responses in HF, with the MIF pathway emerging as a crucial immune regulatory pathway. The CD74/CXCR4 receptor complex in myeloid cell subgroup Mφ2 was significantly upregulated, potentially acting as a crucial regulator in HF. Upon receiving the MIF signal molecule, the CD74/CXCR4 receptor can activate NF-κB signaling to produce chemokines and thereby enhance the inflammatory response. CD74 and CXCR4 may serve as biomarkers and treatment targets for HF.

中文翻译：

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通过单细胞和批量 RNA 测序数据分析确定心力衰竭的关键细胞类型和生物标志物

心力衰竭（HF）是由多种心脏病引起的复杂临床综合征，是世界范围内的重大医学问题。尽管炎症在心力衰竭发病机制中的作用众所周知，但所涉及的特定细胞类型和调节分子仍知之甚少。在这里，我们通过分析从缺血性心肌病和扩张型心肌病这两种主要心衰类型患者获得的单细胞和批量 RNA 测序数据，确定了关键细胞类型和新型生物标志物。通过细胞组分和基因集富集分析，骨髓细胞被确定为参与心力衰竭的主要细胞群。此外，骨髓细胞的差异分析揭示了心力衰竭中细胞通讯和细胞因子调节的免疫反应之间的串扰，其中 MIF 途径成为重要的免疫调节途径。骨髓细胞亚群 M φ 2中的 CD74/CXCR4 受体复合物显着上调，可能作为心力衰竭的关键调节因子。CD74/CXCR4受体接收到MIF信号分子后，可以激活NF- κB信号传导，产生趋化因子，从而增强炎症反应。CD74和CXCR4可以作为心力衰竭的生物标志物和治疗靶点。