Roles of TRIM proteins in cardiovascular diseases: From pathogenesis to therapeutic targeting (Review)

Cardiovascular diseases are driven by sustained mechanical stress, metabolic derangement, inflammation and oxidative injury, which progressively disrupt cellular homeostasis within the heart and vasculature.Although current therapeutic strategies have substantially improved clinical outcomes, most interventions primarily target downstream pathological manifestations rather than upstream regulatory mechanisms that determine stress adaptation and tissue remodeling.Tripartite motif (TRIM) proteins constitute a large family of E3 ubiquitin ligases characterized by a highly conserved RBCC domain architecture and diversified C-terminal regions.By catalyzing distinct ubiquitin chain topologies and functioning as molecular scaffolds, TRIM proteins broadly regulate protein turnover, inflammatory signaling, metabolic adaptation and cell fate determination.Emerging evidence identifies TRIM proteins as context-dependent regulators whose biological effects are shaped by cell type, disease stage and microenvironmental conditions.Multiple TRIM family members have been linked to a wide spectrum of cardiovascular diseases, including atherosclerosis, vascular calcification, myocardial infarction, cardiac hypertrophy and metabolic cardiomyopathy.At the cellular level, TRIM proteins influence disease initiation and progression by modulating endothelial dysfunction, vascular smooth muscle cell phenotypic remodeling, cardiomyocyte survival and metabolic homeostasis, fibroblast activation and immune-inflammatory responses.The present review summarized the biochemical characteristics and cell-specific functions of TRIM proteins and delineates their mechanistic roles in cardiovascular pathogenesis.In addition, it discussed their emerging potential as diagnostic biomarkers and therapeutic targets, highlighting both translational opportunities and context-dependent challenges.Contents 1. Introduction 2. Structural features and classification of TRIM proteins 3. Roles of TRIM proteins in cardiovascular cell types 4. Roles of TRIM proteins in vascular diseases 5. Roles of TRIM proteins in cardiac diseases 6. TRIM proteins as biomarkers and therapeutic targets 7. Conclusions and future perspectives