Extracellular Vesicles in the Heart-Organ Axis: From Inter-Organ Communication to Precision Nanomedicine for Heart...

Heart diseases, including myocardial infarction and heart failure, remain the leading causes of morbidity and mortality worldwide, underscoring an urgent need for innovative diagnostic and therapeutic strategies. In recent years, extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication due to their nanoscale structure, intrinsic bioactivity, and ability to transport diverse molecular cargoes. Increasing evidence demonstrates that EVs are broadly distributed across tissues and organs, where they orchestrate complex inter-organ communication networks. However, the mechanisms by which EV-mediated heart-organ crosstalk regulates cardiovascular disease progression and repair remain incompletely understood. Importantly, EVs are not only endogenous regulators of disease progression but also promising nanocarriers for targeted therapeutic delivery. However, translational challenges remain, particularly in achieving efficient and specific delivery to cardiac tissue following systemic administration. Limited targeting specificity, rapid clearance, insufficient cardiac retention, and EV heterogeneity hinder clinical application, highlighting the need for advanced engineering strategies.

This review followed a systematic literature retrieval framework and searched PubMed, Web of Science, Scopus, and Embase databases from inception to January 2026 using keywords related to EVs, cardiovascular diseases, and interorgan communication. ClinicalTrials.gov was also searched to evaluate the translational progress of EV-based cardiovascular studies.

The reviewed evidence demonstrates that EVs mediate bidirectional communication between the heart and peripheral organs, including brain, gut, liver, kidney, lung, skeletal muscle, bone marrow, spleen, and adipose tissue. Heart- and organ-derived EVs regulate inflammation, metabolism, vascular function, and remodeling through cargo transfer. Stem cell-derived and engineered EVs hold potential for myocardial repair, angiogenesis, immune modulation, and cardiovascular therapy.

EV-mediated heart-organ communication represents an active regulatory mechanism rather than a passive consequence of cardiac injury. Understanding and engineering this network may provide a paradigm for developing precision nanomedicine strategies that target cardiovascular diseases as systemic disorders.