Cardiac Injury Regulates Neuroinflammation Through Extracellular Vesicle-Mediated Heart-Brain Crosstalk

Cognitive impairment is common in heart failure patients, contributing to morbidity and mortality. This impairment may be linked to neuroinflammation in heart failure. However, the primacy of the heart-brain axis remains to be completely understood. Here, we elucidate the potential effects of myocardial injury on pathways and inflammatory mediators responsible for cognitive impairment using a rodent myocardial injury model. The results demonstrate direct extracellular vesicle (EV)-mediated heart-brain crosstalk and the glial uptake of cardiac EVs. In addition, brain inflammation was also elicited following myocardial injury. Moreover, cardiac EVs promote brain microglial cell activation in vitro, potentially mediated by EV-enriched micro-RNAs (miRNAs). miRNA-21 was selectively up-regulated and secreted by cardiac cells under stress via EVs and contributed to a proinflammatory response in microglia in vitro. Under cardiac stress, cardiac-secreted EVs abundant with miRNA-21 communicate with the brain and are associated with microglial activation, which may be responsible for neuroinflammation and neurotoxicity following myocardial injury.