Regulatory Roles of Mitochondrial tRNA-Derived Fragments in Cardiovascular Health and Disease.

Mitochondrial tRNA-derived RNA fragments (mt-tRFs) are small noncoding RNAs generated through specific cleavage. Once considered degradation products, mt-tRFs are now recognized as bioactive regulatory molecules with critical roles in physiological and pathological processes. Given the heart's exceptional mitochondrial density and energy dependence, mt-tRFs serve as important signaling mediators within the mitochondria-nucleus communication network, exhibiting significant potential in maintaining cardiovascular homeostasis and contributing to disease development. This review systematically examines mt-tRF biogenesis, classification, and functional mechanisms, emphasizing their roles in cardiac development and vascular homeostasis. We analyze mt-tRF involvement in major cardiovascular diseases, including mitochondrial cardiomyopathies, cardiac hypertrophy, heart failure, myocardial ischemia-reperfusion injury, hypertension, and pulmonary arterial hypertension, highlighting disease-specific expression profiles and functional consequences. The clinical potential of mt-tRFs as emerging biomarkers and therapeutic targets presents promising opportunities for cardiovascular medicine. Through comprehensive analysis of their regulatory mechanisms and disease associations, this review provides insights into cardiovascular pathogenesis and supports the development of novel diagnostic and therapeutic strategies, positioning mt-tRFs as valuable targets for precision cardiovascular medicine.