文献类型：期刊文献

英文题名：Ubiquitination-mediated protein homeostasis in cardiovascular diseases: molecular mechanisms and therapeutic opportunities

作者：Wang, Yanfei[1];Liu, Xuesong[2];Hu, Yong[3,4,5];Li, Hongfan[6];Li, Zhaoyu[1];Xu, Hui[7];Cheng, Lu[3,4,5];Qiao, Qian[3,4,5];Ye, Xuerui[3,4,5];Zhang, Haoling[8];Song, Zhijing[6,8];Wang, Wei[1,8];Zhang, Jingjing[3,4,5,8]

第一作者：王云飞;王雅菲;王银凤;汪永锋

通信作者：Wang, W[1];Zhang, JJ[2];Zhang, JJ[3];Song, ZJ[4];Zhang, HL[5];Song, ZJ[5];Wang, W[5];Zhang, JJ[5]

机构：[1]Gansu Univ Chinese Med, Coll Acupuncture Moxibust & Tuina, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Basic Med Coll, Lanzhou 730000, Gansu, Peoples R China;[3]Kunming Med Univ, Fuwai Yunnan Hosp, Chinese Acad Med Sci, Affiliated Cardiovasc Hosp, Kunming 650000, Yunnan, Peoples R China;[4]Yunnan Prov Cardiovasc Clin Med Ctr, Kunming 650000, Yunnan, Peoples R China;[5]Yunnan Prov Cardiovasc Clin Med Res Ctr, Kunming 650000, Yunnan, Peoples R China;[6]Gansu Univ Chinese Med, Clin Coll Tradit Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[7]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou 730000, Peoples R China;[8]Univ Sains Malaysia, Adv Med & Dent Inst, Dept Biomed Sci, George Town 13200, Malaysia

第一机构：甘肃中医药大学针灸推拿学院

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Coll Acupuncture Moxibust & Tuina, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Kunming Med Univ, Fuwai Yunnan Hosp, Chinese Acad Med Sci, Affiliated Cardiovasc Hosp, Kunming 650000, Yunnan, Peoples R China;[3]corresponding author), Yunnan Prov Cardiovasc Clin Med Res Ctr, Kunming 650000, Yunnan, Peoples R China;[4]corresponding author), Gansu Univ Chinese Med, Clin Coll Tradit Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[5]corresponding author), Univ Sains Malaysia, Adv Med & Dent Inst, Dept Biomed Sci, George Town 13200, Malaysia.|[10735ccd4a8840d96ab71]甘肃中医药大学中医临床学院;[10735]甘肃中医药大学;[10735db5df93766a96e5b]甘肃中医药大学针灸推拿学院;

年份：2025

卷号：15

期号：6

起止页码：442

外文期刊名：AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE

收录：WOS:【ESCI(收录号:WOS:001659573200003)】；

基金：This study was supported by Science and Technology Department of Yunnan Province-Kunming Medical University, Kunming Medical joint special project-surface project, China, No. 202401AY070001-164; Yunnan Provincial Department of Science and Technology Science and Technology Plan Project-Major Science and Technology Special Projects, China, No. 202405AJ310003; and the Yunnan Pan Xiangbin Expert Workstation under the Yunnan Provincial Project for Scientific and Technological Talents and Platforms Project, No. 202305AF150069.

语种：英文

外文关键词：Cardiovascular diseases; ubiquitination; E3 ligases; deubiquitinating enzymes; protein degradation; signaling pathways; targeted therapy

摘要：Cardiovascular diseases (CVDs) remain one of the leading causes of death worldwide. Although the wellknown risk factors include hypertension, hyperglycemia, dyslipidemia and obesity, the latest studies implicate involvement of pathological mechanisms at the molecular level. Various cellular processes, including oxidative stress, inflammatory response, mitochondrial dysfunction, and ferroptosis, are regarded as contributors to the initiation and progression of CVDs. Ubiquitination, a post-translational modification essential for the maintenance of protein homeostasis, influences the pathogenesis of CVD through regulating protein degradation, signal transduction and cellular functionality. The enzymes E1, E2 and several E3 ligases (e.g., TRAF6, TRIM21, TRIM35) participate in autophagy, inflammation and cardiac remodelling, while deubiquitinating enzymes (DUBs) (e.g., USP25, OTUB1) modulate cardiac function by stabilizing calcium pumps or regulating key signalling molecules. For example, ubiquitination of TRPC3 Ca2+ channels prevents them from functioning closely with phospholipase C; excessive accumulation of TRPC3 lowers cardiac contractility. On the other hand, new protein degradation technologies like Proteolysis-Targeting Chimera (PROTAC) are promising for precise selective down-regulation of disease-related proteins. This study will systematically summarize the molecular mechanisms of ubiquitination in CVDs and its potential therapeutics to provide theoretical support for mechanistic research and the development of new targeted drugs.