Related Experiment Video
Updated: Jun 27, 2026
Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
Alterations of Cerebral Extracellular Vesicle microRNA Profiling Potentially Disrupts Brain Homeostasis Following
Md Monowarul Islam1, Shouyi Liang2, Lijun Sun1
1Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA.
Insights
Heart failure (HF) can cause cognitive impairment (CI). Myocardial infarction alters brain extracellular vesicle (EV) microRNAs, potentially worsening CI by increasing neuroinflammation and oxidative stress via cardiac EVs.
Area of Science:
- Neuroscience
- Cardiology
- Molecular Biology
Background:
- Cognitive impairment (CI) is common in heart failure (HF) patients.
- Oxidative stress and neuroinflammation are key mechanisms underlying CI in HF.
- Extracellular vesicles (EVs) mediate biological signaling and transport microRNAs (miRNAs).
Purpose of the Study:
- To investigate if myocardial injury alters brain EV miRNA profiles.
- To determine if altered brain EV miRNAs contribute to CI by disrupting brain homeostasis.
- To explore the role of cardiac EVs in HF-associated CI.
Main Methods:
- Utilized a rodent myocardial infarction (MI) model.
- Isolated and characterized brain EVs using small RNA sequencing.
- Performed bioinformatic analysis of miRNA profiles.
Main Results:
- Brain EV miRNA profiles changed significantly with HF progression (3, 32, and 65 miRNAs altered at 3, 6, and 12 weeks post-MI, respectively).
- Downregulation of protective miRNAs against oxidative stress and inflammation observed at 6 and 12 weeks.
- Upregulation of miRNAs promoting oxidative stress and neuroinflammation, potentially of cardiac origin.
Conclusions:
- Myocardial injury alters brain EV miRNA profiles, correlating with HF progression.
- Altered miRNAs in brain EVs may contribute to CI by disrupting brain homeostasis.
- Cardiac EVs may play a role in HF-associated CI by influencing brain EV miRNA content.
Abstract:
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.
