Emerging Roles of tRNA-Derived Small RNAs in Cardiovascular Diseases: Mechanistic Insights and Translational Perspectives

Cardiovascular diseases (CVDs) remain the leading cause of disability and mortality worldwide, characterized by highly complex pathophysiological mechanisms involving multilayered gene regulatory networks. Despite substantial advances in related research in recent years, the annual number of CVD-related deaths continues to rise, imposing a profound and persistent global socioeconomic burden. Consequently, there is an urgent need to identify novel molecular mechanisms and therapeutic targets. As an emerging class of non-coding RNAs, tRNA-derived small RNAs (tsRNAs) have increasingly been recognized as pivotal regulators of cardiovascular homeostasis. By targeting RNA, proteins, or other molecular structures, tsRNAs are deeply involved throughout the initiation, progression, and clinical outcomes of CVDs by orchestrating key pathological processes, including mitochondrial dysfunction, metabolic reprogramming, and inflammatory responses. Meanwhile, with ongoing advances in high-throughput sequencing technologies and therapeutic development strategies, the clinical translation of tsRNAs as novel biomarkers and therapeutic targets is also accelerating. Therefore, this review aims to systematically summarize the current core consensus and the latest research advances in this field, comprehensively elucidate the specific mechanisms by which tsRNAs contribute to the pathogenesis and progression of CVDs, and provide innovative insights for the development of more effective translational strategies.