Abstract

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

Document Type

Article

Publication Date

2025

Notes/Citation Information

© 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.jacbts.2025.05.002

Funding Information

This work was supported by the National Institution of Health (grant R01HL153176 to Drs Zucker and Tian), American Heart Association (AHA) Career Development Award (19CDA34520004 to Dr Tian), and AHA Transformational Program Award (24TPA1300008.pc.gr.198448 to Dr Tian). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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