Alcazar-Felix Roberto J, Jhaveri Aditya, Iqbal Javed, Srinath Abhinav, Bennett Carolyn, Bindal Akash, Vera Cruz Diana, Romanos Sharbel, Hage Stephanie, Stadnik Agnieszka, Lee Justine, Lightle Rhonda, Shenkar Robert, Koskimäki Janne, Polster Sean P, Girard Romuald, Awad Issam A
Neurovascular Surgery Program, Department of Neurological Surgery, University of Chicago Medicine and Biological Sciences, Chicago, IL 60637, USA.
Center for Research Informatics, University of Chicago Medicine and Biological Sciences, Chicago, IL 60637, USA.
Int J Mol Sci. 2025 Apr 17;26(8):3794. doi: 10.3390/ijms26083794.
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.
出血性神经血管疾病死亡率高且预后差，迫切需要发现新的生物标志物和治疗靶点。微小核糖核酸（miRNA）是基因表达强有力的转录后调节因子。它们已被研究与疾病状态相关，并参与各种病理过程中的基因相互作用机制。它们在循环体液中的存在和稳定性也表明其具有作为生物标志物的作用。本综述总结了在脑海绵状血管畸形（CCM）背景下关于miRNA的当前知识状态，CCM是一种涉及脑血管畸形和出血且具有已知遗传基础的疾病。我们还回顾了与其他具有脑血管畸形和出血的疾病相比，CCM中常见和独特的miRNA。按照系统评价和Meta分析的首选报告项目指南进行系统检索，查询了截至2025年1月以英文发表的所有同行评审文章，并报告了与四种出血性神经血管疾病相关的miRNA：CCM、动静脉畸形、烟雾病和脑出血。PubMed系统检索获得了154篇符合纳入标准的文章，报道了在这四种出血性神经血管疾病的文献中总共鉴定出267种独特的miRNA。在这267种miRNA中，164种是在临床前研究中鉴定出来的，而159种是在人类受试者中鉴定出来的。17种miRNA在CCM和其他出血性疾病中是共同的。本系统评价中常见和独特的疾病相关miRNA激发了新的机制假说，并在诊断、预测、预后和治疗应用方面具有潜在用途。当前的许多研究可被视为产生假说，反映的是关联而非因果关系。本文提出了未来机制研究的领域以及生物标志物应用背景的分析和临床验证方法。
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