Wang Li, Zhang Yan, Yue Jianming, Zhou Ronghua
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China.
The Research Units of West China (2018RU012)-Chinese Academy of Medical Sciences, West China Hospital, Sichuan University, Chengdu 610041, China.
Int J Mol Sci. 2025 Apr 30;26(9):4260. doi: 10.3390/ijms26094260.
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, with macrophage dysfunction playing a central role in its pathogenesis. Ubiquitination, a critical post-translational modification, regulates diverse macrophage functions, including lipoprotein metabolism, inflammation, oxidative stress, mitophagy, autophagy, efferocytosis, and programmed cell death (pyroptosis, necroptosis, ferroptosis, and apoptosis). This review highlights the regulatory roles of ubiquitination in macrophage-driven CVD progression, focusing on its effects on cholesterol metabolism, inflammation, activation, polarization, and the survival of macrophages. Targeting ubiquitination pathways has therapeutic potential by enhancing macrophage autophagy, reducing inflammation, and improving plaque stability. However, challenges, such as off-target effects, ubiquitination crosstalk, and macrophage heterogeneity, must be addressed. By integrating advances in ubiquitination biology, therapeutic strategies can be developed to mitigate CVD and other macrophage-driven inflammatory diseases. This review underscores the potential of ubiquitination-targeting therapies for mitigating CVD and highlights the key areas for further investigation.
心血管疾病（CVD）是全球发病和死亡的主要原因，巨噬细胞功能障碍在其发病机制中起核心作用。泛素化是一种关键的翻译后修饰，可调节多种巨噬细胞功能，包括脂蛋白代谢、炎症、氧化应激、线粒体自噬、自噬、胞葬作用和程序性细胞死亡（焦亡、坏死性凋亡、铁死亡和凋亡）。本综述强调了泛素化在巨噬细胞驱动的CVD进展中的调节作用，重点关注其对胆固醇代谢、炎症、激活、极化以及巨噬细胞存活的影响。靶向泛素化途径具有治疗潜力，可通过增强巨噬细胞自噬、减轻炎症和改善斑块稳定性来实现。然而，必须解决诸如脱靶效应、泛素化串扰和巨噬细胞异质性等挑战。通过整合泛素化生物学的进展，可以开发出减轻CVD和其他巨噬细胞驱动的炎症性疾病的治疗策略。本综述强调了靶向泛素化治疗减轻CVD的潜力，并突出了进一步研究的关键领域。
