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

• DOI: 10.1007/s00011-023-01817-w
• Publication Date: 2023-12-07T20:01:55Z
• Authors: Yajuan Fu; Juan Zhang; Qiujun Liu; Lan Yang; Qianqian Wu; Xiaomin Yang; Lexin Wang; Ning Ding; Jiantuan Xiong; Yujing Gao; Shengchao Ma; Yideng Jiang
• Keywords: Senescence

Abstract Background Atherosclerosis, characterized by abnormal arterial lipid deposition, is an age-dependent inflammatory disease and contributes to elevated morbidity mortality. Senescent foamy macrophages are considered be deleterious at all stages of atherosclerosis, while the underlying mechanisms remain largely unknown. In this study, we aimed explore senescence-related genes in diagnosis for atherosclerotic plaque progression. Methods The atherosclerosis-related datasets were retrieved from Gene Expression Omnibus (GEO) database, cellular senescence-associated acquired CellAge database. R package Limma was used screen out differentially expressed (DE-SRGs), then three machine learning algorithms applied determine hub DE-SRGs. Next, established a nomogram model further confirm clinical significance Finally, validated expression SRG ABI3 Sc-RNA seq analysis explored mechanism THP-1-derived mouse lesions. Results A total 15 DE-SRGs identified macrophage-rich plaques, with five (ABI3, CAV1, NINJ1, Nox4 YAP1) screened using algorithms. Subsequently, predictive confirmed high validity evaluating Further, upregulated advanced plaques senescent macrophages, which consistent bioinformatics analysis. knockdown abolished macrophage senescence, NF-κB signaling pathway contributed ABI3-mediated senescence. Conclusion We atherogenesis progression unveiled that might promote senescence via activation progression, proposes new preventive therapeutic strategies senolytic agents atherosclerosis.