Extracellular vesicles in the heart failure pathogenesis: mechanisms and therapeutic potential

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, necessitating a deeper understanding of its molecular mechanisms. Extracellular vesicles (EVs) – exosomes, microvesicles, and apoptotic bodies and less-studied subtypes – have emerged as key intercellular communication mediators in cardiovascular diseases. These nanosized particles carry bioactive molecules such as proteins, lipids, and nucleic acids, influencing processes including cardiac remodeling, inflammation, fibrosis, and angiogenesis.

EVs derived from cardiomyocytes, endothelial cells, fibroblasts, and immune cells contribute to HF progression by modulating pathological signaling pathways. For instance, cardiomyocyte-derived EVs may propagate hypertrophy and apoptosis, while fibroblast-derived EVs promote extracellular matrix deposition, leading myocardial stiffness. Conversely, certain EV subpopulations exhibit cardioprotective effects, underscoring their dual role in HF pathogenesis. This review summarizes current knowledge on EV biogenesis, composition, and function in HF, highlighting their diagnostic and therapeutic potential.

We discuss emerging evidence from preclinical and clinical studies, focusing on EV-based biomarkers for early diagnosis and prognosis of HF. Furthermore, we explore therapeutic applications of engineered EVs for targeted drug delivery. Despite considerable advances, unresolved issues such as EV heterogeneity, a lack of standardization isolation methods, and difficulties in applying the results in practice. Addressing these challenges is crucial for unlocking novel strategies for HF management. Integration of fundamental and clinical findings was used to analyze the role of EVs in HF and to evaluate their potential for novel diagnostic and therapeutic applications.

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