Pengfei Yang, Xing Wang, Zhaohui Guo, Chengcheng Ji, Xinbo Zhang
Research in this field is transitioning from mechanistic exploration to clinical translation. China and the United States are the leading contributors, and the intersection of exercise intervention and EVs biology represents the most dynamic research direction. Future efforts should prioritize methodological standardization, large-scale clinical validation, and integration of artificial intelligence approaches, while addressing translational barriers in delivery, manufacturing, regulation, and clinical trial design.
BACKGROUND: Exercise-mediated extracellular vesicle (EV)-derived non-coding RNAs (ncRNAs) contribute to cardiovascular protection, but a systematic synthesis of the field is lacking, and the evolution of research hotspots and knowledge structure remains unclear. This bibliometric study maps the research landscape, frontier hotspots, and emerging trends, while also interpreting the multi-target synergistic mechanisms underlying exercise-mediated cardioprotection based on published evidence.
METHODS: Publications were retrieved from the Web of Science Core Collection, PubMed, and Scopus from database inception to April 3, 2026. After deduplication and screening, 188 articles were included. VOSviewer, CiteSpace, and the R-based Bibliometrix package were employed for analyses of countries, institutions, journals, highly cited papers, and keywords.
RESULTS: Annual publications grew from 1 in 2013 to 28 in 2025. China (65 publications) and the United States (48 publications) together contributed over 60% of the total. Core journals included Frontiers in Physiology (11 publications), International Journal of Molecular Sciences (9 publications), and Cells (8 publications). Research evolved in three phases: early multi-directional exploration (2015-2020), a middle phase converging on EV-centric themes (2021-2023), and a recent return to fundamental biology (2023-2026). "Extracellular vesicles" ranked first in frequency (48 occurrences), while "physical activity" had the highest centrality (centrality 0.22). Ten keyword clusters were identified, with "aerobic exercise," "animal model," and "human cell" emerging as recent burst keywords. Mechanistically, informed by bibliometric patterns and published preclinical evidence, we propose that exercise may exert anti-apoptotic, antioxidant, anti-inflammatory, and anti-fibrotic effects by engaging a potential synergistic network involving EV-derived ncRNAs, though this framework requires experimental validation.
CONCLUSION: Research in this field is transitioning from mechanistic exploration to clinical translation. China and the United States are the leading contributors, and the intersection of exercise intervention and EVs biology represents the most dynamic research direction. Future efforts should prioritize methodological standardization, large-scale clinical validation, and integration of artificial intelligence approaches, while addressing translational barriers in delivery, manufacturing, regulation, and clinical trial design.