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 underlying mechanisms of CI. The role of extracellular vesicles (EVs) as effective communicators of biological signaling in myocardial function has been extensively investigated. EVs are well-known to transport a variety of microRNAs (miRNAs), however, it is unclear if myocardial injury alters the miRNA profiling of brain EVs which may contribute to CI by disrupting brain homeostasis. Using a rodent myocardial infarction (MI) model, we isolated brain EVs, and characterized their miRNA profiling by small RNA sequencing. Our results demonstrate that miRNA profiling in brain EVs varies with the progression of HF. Only three miRNAs were significantly changed at 3wks post-MI, thirty-two miRNAs demonstrate significant changes at 6wks post-MI, and sixty-five miRNAs show significant alterations at 12wks post-MI. Bioinformatic analysis suggests that some miRNAs against oxidative stress and inflammation were downregulated in brain EVs following 6wks post-MI, whereas several miRNAs responsible for oxidative stress and neuroinflammation were significantly increased, which may be cardiac in origin following MI. Collectively, cardiac EVs may contribute to the miRNA alterations in brain EVs, potentially contributing to CI by disrupting brain homeostasis.