Unveiling the role of ABI3 and hub senescence-related genes in macrophage senescence for atherosclerotic plaque progression

作者：Yajuan Fu, Juan Zhang, Qiujun Liu, Lan Yang, Qianqian Wu, Xiaomin Yang, Lexin Wang, Ning Ding, Jiantuan Xiong, Yujing Gao, Shengchao Ma, Yideng Jiang · 发表于：Inflammation Research · 年份：2023 · DOI：10.1007/s00011-023-01817-w · 被引用次数：16 · 研究领域：Hippo pathway signaling and YAP/TAZ、Telomeres, Telomerase, and Senescence、Immune cells in cancer

BACKGROUND: Atherosclerosis, characterized by abnormal arterial lipid deposition, is an age-dependent inflammatory disease and contributes to elevated morbidity and mortality. Senescent foamy macrophages are considered to be deleterious at all stages of atherosclerosis, while the underlying mechanisms remain largely unknown. In this study, we aimed to explore the senescence-related genes in macrophages diagnosis for atherosclerotic plaque progression. METHODS: The atherosclerosis-related datasets were retrieved from the Gene Expression Omnibus (GEO) database, and cellular senescence-associated genes were acquired from the CellAge database. R package Limma was used to screen out the differentially expressed senescence-related genes (DE-SRGs), and then three machine learning algorithms were applied to determine the hub DE-SRGs. Next, we established a nomogram model to further confirm the clinical significance of hub DE-SRGs. Finally, we validated the expression of hub SRG ABI3 by Sc-RNA seq analysis and explored the underlying mechanism of ABI3 in THP-1-derived macrophages and mouse atherosclerotic lesions. RESULTS: A total of 15 DE-SRGs were identified in macrophage-rich plaques, with five hub DE-SRGs (ABI3, CAV1, NINJ1, Nox4 and YAP1) were further screened using three machine learning algorithms. Subsequently, a nomogram predictive model confirmed the high validity of the five hub DE-SRGs for evaluating atherosclerotic plaque progression. Further, the ABI3 expression was upre...