Extracellular Vesicles in Cardiovascular Disease: Biomarkers, Therapeutic Applications, and Drug Delivery Strategies Publisher Pubmed



Abuhassan Q ; Salajegheh A ; Muhammad FA ; Alhussainy AF ; Gajjar TB ; Hanumanthayya M ; Shukla SK ; Panigrahi R ; Bainsal N ; Polatova D ; Sameer HN ; Salih RM ; Adil M
Source: Clinica Chimica Acta Published:2026

Abstract

Extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication in cardiovascular disease (CVD), influencing inflammation, thrombosis, fibrosis, angiogenesis, and cardiac remodeling through the transfer of proteins, lipids, and RNAs. The presence of EVs in virtually all biofluids and their cargo's close linkage to cellular activation or injury make EVs attractive noninvasive biomarkers for CVD diagnosis, prognosis, and therapy monitoring, with circulating EV signatures reported in myocardial infarction, heart failure, atherosclerosis, and valvular and cardiomyopathic disorders. Parallel advances highlight EVs as cell-free therapeutic agents, recapitulating key paracrine benefits of stem and progenitor cell therapies while avoiding issues of low engraftment and arrhythmogenic risk. In addition to their endogenous activity, both native and engineered EVs are being actively developed as drug delivery platforms, offering biocompatibility, immune stealth, and the capacity to cross biological barriers, with promising data for targeted delivery to the ischemic myocardium and atherosclerotic plaques. Engineering strategies, including surface functionalization, controlled cargo loading, and combination with biomaterials such as hydrogels, can increase cardiac homing, prolong circulation, and improve on-target efficacy. Despite this promise, major hurdles remain: heterogeneity of EV subtypes, lack of standardized isolation and characterization workflows, low production yields, incomplete pharmacokinetic understanding, and unresolved regulatory classification. Addressing these limitations through multi-omics, advanced bioengineering, scalable bioprocessing, and rigorously designed clinical trials will be critical to integrate EV-based biomarkers, therapeutics, and delivery systems into cardiovascular precision medicine. © 2026 Elsevier B.V.