Nie Wenyang, Wang Yong, Xiao Yuanyuan, Lin Zhiheng, Zhang Jingwen, Zhao Zhijie, Wang Zhen
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, 16369 Jingshi Rd, Jinan, 250014, China.
Department of Cardiovascular Diseases, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Rd, Jinan, 250014, China.
Sci Rep. 2025 Jul 27;15(1):27331. doi: 10.1038/s41598-025-09928-6.
Cardiomyopathy encompasses a range of diseases that severely affect the complex functions of the heart, involving structural and functional abnormalities, and is associated with high mortality. Recent studies have highlighted the critical role of ferroptosis in regulating oxidative stress and inflammation in cardiomyopathy. In this study, we established that the C6 S100A4+ SMCs subpopulation is critical by performing an integrated single-cell analysis of the known publicly available data GSE145154. We validated the role of S100A4 in SMCs through in vitro experiments, providing evidence for its potential as a therapeutic target. Furthermore, these cells interact with endothelial cells through the PTN-NCL pathway, influencing disease progression. Key transcription factors, including KLF2, FOS, FOSB, and JUNB, were identified. This key subpopulation, along with its associated signaling pathways, marker genes, stemness genes, and transcription factors, may offer new insights for preventing the onset and progression of cardiomyopathy, particularly ischemic cardiomyopathy.
心肌病包括一系列严重影响心脏复杂功能的疾病，涉及结构和功能异常，且与高死亡率相关。最近的研究强调了铁死亡在调节心肌病中的氧化应激和炎症方面的关键作用。在本研究中，我们通过对已知的公开可用数据GSE145154进行综合单细胞分析，确定了C6 S100A4+ 平滑肌细胞亚群至关重要。我们通过体外实验验证了S100A4在平滑肌细胞中的作用，为其作为治疗靶点的潜力提供了证据。此外，这些细胞通过PTN-NCL途径与内皮细胞相互作用，影响疾病进展。鉴定出了包括KLF2、FOS、FOSB和JUNB在内的关键转录因子。这个关键亚群及其相关的信号通路、标记基因、干性基因和转录因子，可能为预防心肌病尤其是缺血性心肌病的发生和发展提供新的见解。
