Extracellular vesicles in heart failure: bridging pathogenic insights, diagnostic utility, and therapeutic applications

Heart failure (HF), the terminal stage of most cardiovascular diseases, remains a major global health burden with limited therapeutic options that do not fully achieve myocardial repair or functional recovery. Extracellular vesicles (EVs), nanoscale membrane-bound particles released by cells, have been increasingly recognized as important mediators in the pathophysiology of HF and as potential therapeutic targets. As intercellular messengers carrying bioactive molecules, including proteins, lipids, and non-coding RNAs, EVs regulate gene expression and functional states in recipient cells. This review summarizes current evidence on the roles of EVs in key pathological processes of HF, including inflammation, mitochondrial dysfunction, myocardial hypertrophy, fibrosis, apoptosis, and angiogenesis. We also discuss their potential as circulating biomarkers for the diagnosis and prognosis of HF. In addition, we describe emerging therapeutic strategies, including stem cell-derived EVs and engineered EVs as delivery platforms for therapeutic molecules. Furthermore, we discuss the pharmacological implications of EVs in current heart failure treatment paradigms, highlighting their potential role in bridging mechanistic insights with clinical therapeutic strategies. Collectively, these findings highlight the relevance of EVs in HF research and suggest directions for future investigation.