Chen Yali, Wang Yihuan, Wu Tingting, Guo Xiaolei, Bai Xueyang, Wang Lirui, Yan Peipei, Zheng Zhe, Xiao Lili, Li Ling
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China.
Cardiovasc Toxicol. 2025 Jun 26. doi: 10.1007/s12012-025-10007-5.
Atherosclerosis (AS) is a fundamental pathological process underlying cardiovascular disease (CVD), which begins with dysfunction in the endothelial system resulting from damage to vascular endothelial cells. Our research demonstrates that the deubiquitinating enzyme USP5 is upregulated in endothelial cells of AS plaques. In vitro, USP5 knockdown enhanced cell viability, whereas attenuated ox-LDL-induced apoptosis, oxidative stress, inflammation, and endothelial dysfunction in HUVECs. In vivo studies in a mouse model of atherosclerosis showed that USP5 inhibition significantly reduced plaque formation, collagen deposition, and inflammatory cell infiltration. Protein mass spectrometry analysis and immunoprecipitation assays show that USP5 interacts with programmed cell death 4 (PDCD4). PDCD4 overexpression rescues USP5 knockdown effects on HUVECs exposed to ox-LDL. This study elucidates the biological functions of the USP5/PDCD4 axis in the injury of cells of the vascular endothelium during AS and suggests that targeting this axis could offer a potential therapeutic strategy for atherosclerosis.
动脉粥样硬化（AS）是心血管疾病（CVD）的一个基本病理过程，它始于血管内皮细胞受损导致的内皮系统功能障碍。我们的研究表明，去泛素化酶USP5在AS斑块的内皮细胞中上调。在体外，敲低USP5可增强细胞活力，同时减轻氧化型低密度脂蛋白（ox-LDL）诱导的人脐静脉内皮细胞（HUVECs）凋亡、氧化应激、炎症和内皮功能障碍。在动脉粥样硬化小鼠模型中的体内研究表明，抑制USP5可显著减少斑块形成、胶原沉积和炎性细胞浸润。蛋白质质谱分析和免疫沉淀试验表明，USP5与程序性细胞死亡4（PDCD4）相互作用。PDCD4过表达可挽救USP5敲低对暴露于ox-LDL的HUVECs的影响。本研究阐明了USP5/PDCD4轴在AS期间血管内皮细胞损伤中的生物学功能，并表明靶向该轴可能为动脉粥样硬化提供一种潜在的治疗策略。
