This study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidental deaths through autopsy. A total of 2784 proteins were obtained from label-free quantitative proteomic analysis. This included a total of 265 differential proteins which were involved in SCD-related processes, such as inflammation, muscle system process regulation, metal ion transport, and lysosomal pathway. Western blotting was carried out to measure the expressions of cathepsin C (CTSC), focal adhesion kinase (FAK), p-FAK, and proteins related to the p38/MAPK signaling pathway, whereas immunohistochemistry was performed to determine the localization and expression of CTSC, TNF-α, and CD206 in arterial tissues. It was found that CTSC were the most expressed proteins with a significant upward trend in SCD cases. Besides, CTSC regulated macrophage polarization to M1 through the FAK-induced p38/MAPK signaling pathway. This promoted the release of inflammatory factors and eventually increased the inflammatory response. In conclusion, this study implies that CTSC may be one of the key molecular targets for promoting macrophage M1 polarization in SCD, which may provide new therapeutic insights into the treatment of inflammatory diseases.

中文翻译：

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组织蛋白酶 C 在心源性猝死中通过 p38/MAPK 通路参与巨噬细胞 M1 极化

本研究旨在确定与心源性猝死 (SCD) 发病机制相关的分子标志物。它提供了通过组织学检查诊断为 SCD 的受试者和通过尸检诊断为非疾病意外死亡病例的人类左冠状动脉前降支的蛋白质组学分析。从无标记定量蛋白质组学分析中总共获得了 2784 种蛋白质。这包括总共 265 种参与 SCD 相关过程的差异蛋白，例如炎症、肌肉系统过程调节、金属离子转运和溶酶体途径。Western blotting检测组织蛋白酶C（CTSC）、粘着斑激酶（FAK）、p-FAK和p38/MAPK信号通路相关蛋白的表达，α和 CD206 在动脉组织中。发现CTSC是SCD病例中表达最多的具有显着上升趋势的蛋白质。此外，CTSC 通过 FAK 诱导的 p38/MAPK 信号通路调节巨噬细胞向 M1 极化。这促进了炎症因子的释放，最终增加了炎症反应。总之，本研究表明CTSC可能是促进SCD巨噬细胞M1极化的关键分子靶点之一，这可能为炎症性疾病的治疗提供新的治疗见解。