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Volume 16
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Article

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

by
Md Monowarul Islam
1,†,
Shouyi Liang
2,†,
Lijun Sun
1,
Guoku Hu
3,
Neha Dhyani
4,
Lie Gao
5,
Tara L. Rudebush
4,
Xue Xu
1,
Jinpeng Liu
2,
Irving H. Zucker
4 and
Changhai Tian
1,*
1
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA
2
Department of Cancer Biostatistics, University of Kentucky, Lexington, KY 40536, USA
3
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
4
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
5
Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2026, 16(6), 776; https://doi.org/10.3390/biom16060776
Submission received: 4 May 2026 / Revised: 21 May 2026 / Accepted: 23 May 2026 / Published: 26 May 2026
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Potential of Extracellular Vesicles in Neurovascular Diseases)
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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.
Keywords: heart failure; cognitive impairment; cerebral extracellular vesicle; oxidative stress; neuroinflammation heart failure; cognitive impairment; cerebral extracellular vesicle; oxidative stress; neuroinflammation

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MDPI and ACS Style

Islam, M.M.; Liang, S.; Sun, L.; Hu, G.; Dhyani, N.; Gao, L.; Rudebush, T.L.; Xu, X.; Liu, J.; Zucker, I.H.; et al. Alterations of Cerebral Extracellular Vesicle microRNA Profiling Potentially Disrupts Brain Homeostasis Following Myocardial Infarction. Biomolecules 2026, 16, 776. https://doi.org/10.3390/biom16060776

AMA Style

Islam MM, Liang S, Sun L, Hu G, Dhyani N, Gao L, Rudebush TL, Xu X, Liu J, Zucker IH, et al. Alterations of Cerebral Extracellular Vesicle microRNA Profiling Potentially Disrupts Brain Homeostasis Following Myocardial Infarction. Biomolecules. 2026; 16(6):776. https://doi.org/10.3390/biom16060776

Chicago/Turabian Style

Islam, Md Monowarul, Shouyi Liang, Lijun Sun, Guoku Hu, Neha Dhyani, Lie Gao, Tara L. Rudebush, Xue Xu, Jinpeng Liu, Irving H. Zucker, and et al. 2026. "Alterations of Cerebral Extracellular Vesicle microRNA Profiling Potentially Disrupts Brain Homeostasis Following Myocardial Infarction" Biomolecules 16, no. 6: 776. https://doi.org/10.3390/biom16060776

APA Style

Islam, M. M., Liang, S., Sun, L., Hu, G., Dhyani, N., Gao, L., Rudebush, T. L., Xu, X., Liu, J., Zucker, I. H., & Tian, C. (2026). Alterations of Cerebral Extracellular Vesicle microRNA Profiling Potentially Disrupts Brain Homeostasis Following Myocardial Infarction. Biomolecules, 16(6), 776. https://doi.org/10.3390/biom16060776

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