Fei Xiangyu, Song Chao, Cui Jian, Li Yuqing, Lei Xiaoyong, Tang Huifang
School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, Hunan, China.
Hunan Provincial Key Laboratory of Multi-omics And Artificial Intelligence of Cardiovascular Diseases, University of South China, Hengyang, Hunan, China.
Front Cardiovasc Med. 2025 May 1;12:1582049. doi: 10.3389/fcvm.2025.1582049. eCollection 2025.
Cardiovascular diseases (CVDs) have become the leading cause of death globally, surpassing infectious diseases and other chronic illnesses. The incidence and mortality rates of CVDs are rising worldwide, posing a key challenge in public health. The ubiquitination system is a vast and complex. It is an important post-translational modification that plays a crucial role in various cellular processes. Deubiquitination is catalyzed by deubiquitinases (DUBs), which remove ubiquitin (Ub) from ubiquitinated proteins, thereby reversing the ubiquitination process. DUBs play an important role in many biological processes, such as DNA repair, cell metabolism, differentiation, epigenetic regulation, and protein stability control. They also participate in the regulation of many signaling pathways associated with the development and progression of CVDs. In this review, we primarily focus on the role of DUBs in various key pathological mechanisms of atherosclerosis (AS), such as foam cell formation, vascular remodeling (VR), endothelial-to-mesenchymal transition (End-MT), and clonal hematopoiesis (CH). In the heart, we summarize the involvement of DUBs in diseases and pathological processes, including heart failure (HF), myocardial infarction (MI), myocardial hypertrophy (MH) and ischemia/reperfusion (I/R) injury. Additionally, we also explore the diabetic cardiomyopathy (DCM) and the use of doxorubicin-induced cardiotoxicity in clinical settings. A comprehensive understanding of deubiquitination may provide new insights for the treatment and drug design of CVDs.
心血管疾病（CVDs）已成为全球主要死因，超过了传染病和其他慢性疾病。全球范围内，心血管疾病的发病率和死亡率都在上升，这对公共卫生构成了关键挑战。泛素化系统庞大而复杂。它是一种重要的翻译后修饰，在各种细胞过程中发挥着关键作用。去泛素化由去泛素酶（DUBs）催化，这些酶从泛素化蛋白质中去除泛素（Ub），从而逆转泛素化过程。去泛素酶在许多生物学过程中发挥重要作用，如DNA修复、细胞代谢、分化、表观遗传调控和蛋白质稳定性控制。它们还参与许多与心血管疾病发生发展相关信号通路的调控。在本综述中，我们主要关注去泛素酶在动脉粥样硬化（AS）各种关键病理机制中的作用，如泡沫细胞形成、血管重塑（VR）、内皮-间充质转化（End-MT）和克隆性造血（CH）。在心脏方面，我们总结了去泛素酶在疾病和病理过程中的参与情况，包括心力衰竭（HF）、心肌梗死（MI）、心肌肥大（MH）和缺血/再灌注（I/R）损伤。此外，我们还探讨了糖尿病心肌病（DCM）以及阿霉素诱导的心脏毒性在临床中的应用。对去泛素化的全面理解可能为心血管疾病的治疗和药物设计提供新的见解。
