Alterations of Cerebral Extracellular Vesicle microRNA Profiling Potentially Disrupts Brain Homeostasis Following Myocardial Infarction.

Cognitive impairment (CI) is prevalent among heart failure (HF) patients. Although the brain injury in HF is multifactorial, oxidative stress and neuroinflammation are common pathological features of neurological disorders and are increasingly recognized as key mechanisms underlying CI. Extracellular vesicles (EVs) are well-established mediators of biological signaling in myocardial function and are widely recognized for transporting a variety of microRNAs. However, whether myocardial injury alters the miRNA profiles of brain EVs, potentially contributing to cognitive impairment (CI) by disrupting brain homeostasis, remains poorly understood. Using a rodent myocardial infarction (MI) model, we isolated brain EVs and characterized their miRNA profiling by means of small RNA sequencing. Our results demonstrate that miRNA profiles in brain EVs vary with HF progression. Only three miRNAs were significantly changed at 3 weeks post-MI, whereas thirty-two miRNAs and sixty-five miRNAs demonstrated significant changes post-MI, showed significant alterations at 6 and 12 weeks post-MI, respectively. Bioinformatic analysis suggests that some miRNAs against oxidative stress and inflammation were downregulated in brain EVs at 6 and 12 weeks post-MI. Conversely, several miRNAs responsible for oxidative stress and neuroinflammation were significantly increased, which may be of cardiac origin following MI. Collectively, these findings suggest that cardiac EVs may contribute to miRNA alterations in brain EVs, potentially driving CI by disrupting brain homeostasis.