Ageing Research Reviews · Jun 25, 2026
Ubiquitination in cardiovascular diseases: From molecular mechanisms to therapeutic targeting
By Wang JY, Zhang TN, Yang N et al.
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, with ageing constituting a major underlying risk factor. Ubiquitination, a highly conserved and reversible posttranslational modification, has emerged as a pivotal regulator of CVDs through the modulation of target proteins through various mechanisms, including protein stability, activity, subcellular localization, and molecular interactions. This process is orchestrated by ubiquitin-activating (E1), conjugating (E2), and ligating (E3) enzymes, which attach ubiquitin to target proteins, as well as by deubiquitinases (DUBs), which remove ubiquitin, thereby enabling the dynamic and reversible control of proteins. Through these mechanisms, ubiquitination plays vital roles in diverse cellular processes that are central to cardiovascular homeostasis. Accumulating evidence indicates that the dysregulation of ubiquitination plays pivotal roles in the initiation and progression of various cardiovascular diseases. In this review, we provide a comprehensive overview of the components and molecular mechanisms of ubiquitination and discuss its roles and underlying mechanisms in various cardiovascular conditions. Specially, we summarize the regulatory roles of ageing in cardiovascular disease and its regulation by ubiquitination. We also highlight common regulatory pathways underlying ubiquitination-mediated cardiovascular diseases. Furthermore, we review recent advances in ubiquitination-targeted therapeutic strategies, including those targeting ubiquitin ligases, deubiquitinases, and the ubiquitin-proteasome system, and discuss translational challenges and future directions. We also summarize their applications in cardiovascular diseases. In conclusion, this manuscript aims to offer an integrated understanding of ubiquitination-mediated cardiovascular pathology, providing the basis for the development of novel therapeutic approaches targeting ubiquitination.