Wang Li-Rong, Zhang Chun-Xi, Tian Lv-Bo, Huang Jie, Jia Li-Jun, Tao Hao, Yu Neng-Wei, Li Bing-Hu
Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
University of Electronic Science and Technology of China, Chengdu, 610054, China.
Mamm Genome. 2025 Mar 28. doi: 10.1007/s00335-025-10124-0.
The mitochondria-associated endoplasmic reticulum membrane is implicated in atherosclerosis (AS). However, its precise molecular mechanisms remain undefined. This study identified KLRC1 and SOCS2 as key protective genes against AS through transcriptomic analysis integrated with Mendelian randomization. Both genes exhibited significantly reduced expression in the AS group. Immune infiltration analysis revealed a strong positive correlation between activated CD8 T cells and these genes, while eosinophils displayed the most pronounced negative correlation with KLRC1, and regulatory T cells exhibited the strongest negative association with SOCS2. Notably, SOCS2 emerged as a pivotal protective factor, offering novel insights into AS pathogenesis and providing a robust theoretical foundation for early diagnosis and potential therapeutic strategies.
线粒体相关内质网膜与动脉粥样硬化(AS)有关。然而,其确切的分子机制仍不明确。本研究通过整合孟德尔随机化的转录组分析,确定KLRC1和SOCS2为抗AS的关键保护基因。这两个基因在AS组中的表达均显著降低。免疫浸润分析显示,活化的CD8 T细胞与这些基因之间存在强正相关,而嗜酸性粒细胞与KLRC1的负相关性最为明显,调节性T细胞与SOCS2的负相关性最强。值得注意的是,SOCS2成为一个关键的保护因子,为AS发病机制提供了新的见解,并为早期诊断和潜在治疗策略提供了坚实的理论基础。