Extracellular vesicles in the heart: mediators of intercellular communication in health and disease in vitro

Extracellular vesicles (EVs) have gained recognition as important mediators of intercellular communication in the heart. In general, intercellular communication is essential for coordinating cardiac function, enabling cells to respond to physiological environment and pathological stress. The myocardium is primarily composed of cardiomyocytes, while cardiac fibroblasts, endothelial cells, and resident immune cells represent the most abundant non-myocyte populations, collectively maintaining cardiac structure and function. EVs, secreted by different cardiac cells, carry proteins, nucleic acids and lipids that reflect the state of the producing cells and influence the function of recipient cells. In the healthy myocardium, EVs contribute to physiological remodeling and angiogenesis. Under pathological stressors such as ischemia, inflammation, or fibrosis, their cargo and functions change markedly, promoting maladaptive and regenerative responses. This review summarizes current knowledge generated from in vitro studies on the role of cardiac EVs in intercellular communication, focusing on how their origin and cargo determine their functional impact. Cardiac EVs represent essential regulators of cellular crosstalk in both physiological and pathological settings. By integrating environmental signals and transferring bioactive cargo between cardiac cells, they can either preserve tissue homeostasis or contribute to maladaptive remodeling. A deeper understanding of their crosstalk mechanisms offers opportunities for novel therapeutic strategies and biomarker discovery in heart disease. • EVs are critical mediators of intercellular signaling in the heart. They carry molecular cargo that can support homeostasis or contribute to disease. • EV-mediated cardiac communication is multi-directional and versatile, coordinating transcriptional, metabolic, and structural processes among heterogeneous cell populations. • Understanding cell type-specific cargo shifts under pathological conditions is essential for biomarker discovery and therapy. • EV heterogeneity and context-dependent effects pose translational challenges. Rational engineering and validation are critical for clinical translation. • Integration of in vitro mechanistic studies with in vivo validation is crucial for translational impact.