The role of extracellular vesicles in cell–cell crosstalk in cardiotoxicity

Cardiotoxicity can be a result of the action of various therapeutic drugs, including anti-cancer drugs, and can pose a greater risk to patients' health than the underlying disease being treated. As cardiac function relies on the interplay between different cell types, dysfunction in cell-cell crosstalk can promote disease-associated mechanisms. Extracellular vesicles (EVs) are lipid bilayer structures that provide a means of cell-cell communication via delivery of bioactive cargo. EVs contribute to both physiology and pathophysiology, having recently been implicated in the pathogenesis of cardiovascular diseases (CVDs). Cardiotoxicity displays pathological similarities to those seen in numerous CVDs, suggesting a potential role for EVs in this process. This role has been confirmed in studies on the anti-cancer drug doxorubicin, observing that EVs generated by doxorubicin-treated cancer cells can drive cardiotoxicity in healthy cells present in the cardiovascular system. Conversely, EVs have also shown therapeutic potential in treating cardiovascular pathologies. EVs, such as those originating from stem cells, have been observed to disrupt pathogenesis of CVD and doxorubicin-induced cardiotoxicity, suggesting potential for EV-based therapeutics. As current therapeutic strategies tackling cardiotoxicity treat late-stage pathological changes and have limited long-term efficacy, therapeutics targeting mechanisms that initiate and drive cardiotoxicity may be more effective in preserving cardiac function. Overall, this review demonstrates the potential contribution of EVs in cardiovascular (patho)physiology through mediating cell-cell communication. This review aims to highlight the need for further study to fully understand the significance of EVs in driving drug-induced cardiotoxicity and includes suggestions for methods of establishing accessible EV-based therapeutics for at-risk patients.