Mechanisms and Translational Potential of Plant-Derived Extracellular Vesicles in Cardiovascular Disease.

Cardiovascular diseases remain a major global health burden. Plant-derived extracellular vesicles (PDEVs) are increasingly being investigated as potential therapeutic and drug-delivery platforms for cardiovascular disease. PDEVs are natural nanovesicles carrying bioactive lipids, proteins, nucleic acids, and phytochemicals. Preclinical studies suggest that selected PDEV preparations may exert protective effects in cardiovascular disease-related models by modulating inflammation, oxidative stress, lipid metabolism, and endothelial repair. In experimental models, selected PDEVs have shown preliminary improvements in cargo stability, lesion accumulation, controlled release, and local retention through drug loading, surface ligand modification, responsive design, and integration with biomaterials. This review summarises the biogenesis, isolation, characterisation, and cardiovascular actions of PDEVs, with emphasis on their engineering and targeted delivery applications in atherosclerosis, myocardial infarction, ischaemia-reperfusion injury, vascular calcification, restenosis, and cardiotoxicity. Current challenges, including insufficient standardization, uncertain regulatory classification, unclear mechanisms, and limited pharmacokinetic and long-term safety data, are also discussed. Addressing these issues is essential for reliably evaluating the clinical translation potential of PDEVs.