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Review

A Systematic Review of MicroRNAs in Hemorrhagic Neurovascular Disease: Cerebral Cavernous Malformations as a Paradigm

by
Roberto J. Alcazar-Felix
1,
Aditya Jhaveri
1,
Javed Iqbal
1,
Abhinav Srinath
1,
Carolyn Bennett
1,
Akash Bindal
1,
Diana Vera Cruz
2,
Sharbel Romanos
1,
Stephanie Hage
1,
Agnieszka Stadnik
1,
Justine Lee
1,
Rhonda Lightle
1,
Robert Shenkar
1,
Janne Koskimäki
1,
Sean P. Polster
1,
Romuald Girard
1,† and
Issam A. Awad
1,*,†
1
Neurovascular Surgery Program, Department of Neurological Surgery, University of Chicago Medicine and Biological Sciences, Chicago, IL 60637, USA
2
Center for Research Informatics, University of Chicago Medicine and Biological Sciences, Chicago, IL 60637, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(8), 3794; https://doi.org/10.3390/ijms26083794
Submission received: 5 March 2025 / Revised: 7 April 2025 / Accepted: 16 April 2025 / Published: 17 April 2025
(This article belongs to the Special Issue Molecular Mechanisms and Emerging Therapies in Neurovascular Disease)
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Abstract

Hemorrhagic neurovascular diseases, with high mortality and poor outcomes, urge novel biomarker discovery and therapeutic targets. Micro-ribonucleic acids (miRNAs) are potent post-transcriptional regulators of gene expression. They have been studied in association with disease states and implicated in mechanistic gene interactions in various pathologies. Their presence and stability in circulating fluids also suggest a role as biomarkers. This review summarizes the current state of knowledge about miRNAs in the context of cerebral cavernous malformations (CCMs), a disease involving cerebrovascular dysmorphism and hemorrhage, with known genetic underpinnings. We also review common and distinct miRNAs of CCM compared to other diseases with brain vascular dysmorphism and hemorrhage. A systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, queried all peer-reviewed articles published in English as of January 2025 and reported miRNAs associated with four hemorrhagic neurovascular diseases: CCM, arteriovenous malformations, moyamoya disease, and intracerebral hemorrhage. The PubMed systematic search retrieved 154 articles that met the inclusion criteria, reporting a total of 267 unique miRNAs identified in the literature on these four hemorrhagic neurovascular diseases. Of these 267 miRNAs, 164 were identified in preclinical studies, while 159 were identified in human subjects. Seventeen miRNAs were common to CCM and other hemorrhagic diseases. Common and unique disease-associated miRNAs in this systematic review motivate novel mechanistic hypotheses and have potential applications in diagnostic, predictive, prognostic, and therapeutic contexts of use. Much of current research can be considered hypothesis-generating, reflecting association rather than causation. Future areas of mechanistic investigation are proposed alongside approaches to analytic and clinical validations of contexts of use for biomarkers.
Keywords: cerebral cavernous malformation; microRNAs; biomarkers; systematic review; hemorrhage; neurovascular diseases cerebral cavernous malformation; microRNAs; biomarkers; systematic review; hemorrhage; neurovascular diseases

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MDPI and ACS Style

Alcazar-Felix, R.J.; Jhaveri, A.; Iqbal, J.; Srinath, A.; Bennett, C.; Bindal, A.; Vera Cruz, D.; Romanos, S.; Hage, S.; Stadnik, A.; et al. A Systematic Review of MicroRNAs in Hemorrhagic Neurovascular Disease: Cerebral Cavernous Malformations as a Paradigm. Int. J. Mol. Sci. 2025, 26, 3794. https://doi.org/10.3390/ijms26083794

AMA Style

Alcazar-Felix RJ, Jhaveri A, Iqbal J, Srinath A, Bennett C, Bindal A, Vera Cruz D, Romanos S, Hage S, Stadnik A, et al. A Systematic Review of MicroRNAs in Hemorrhagic Neurovascular Disease: Cerebral Cavernous Malformations as a Paradigm. International Journal of Molecular Sciences. 2025; 26(8):3794. https://doi.org/10.3390/ijms26083794

Chicago/Turabian Style

Alcazar-Felix, Roberto J., Aditya Jhaveri, Javed Iqbal, Abhinav Srinath, Carolyn Bennett, Akash Bindal, Diana Vera Cruz, Sharbel Romanos, Stephanie Hage, Agnieszka Stadnik, and et al. 2025. "A Systematic Review of MicroRNAs in Hemorrhagic Neurovascular Disease: Cerebral Cavernous Malformations as a Paradigm" International Journal of Molecular Sciences 26, no. 8: 3794. https://doi.org/10.3390/ijms26083794

APA Style

Alcazar-Felix, R. J., Jhaveri, A., Iqbal, J., Srinath, A., Bennett, C., Bindal, A., Vera Cruz, D., Romanos, S., Hage, S., Stadnik, A., Lee, J., Lightle, R., Shenkar, R., Koskimäki, J., Polster, S. P., Girard, R., & Awad, I. A. (2025). A Systematic Review of MicroRNAs in Hemorrhagic Neurovascular Disease: Cerebral Cavernous Malformations as a Paradigm. International Journal of Molecular Sciences, 26(8), 3794. https://doi.org/10.3390/ijms26083794

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