Mamiya Takashi, Kanamori Fumiaki, Yokoyama Kinya, Ota Akinobu, Karnan Sivasundaram, Uda Kenji, Araki Yoshio, Maesawa Satoshi, Yoshikawa Kazuhiro, Saito Ryuta
1Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya.
2Department of Biochemistry, Aichi Medical University School of Medicine, and.
J Neurosurg. 2022 Jul 29;138(3):709-716. doi: 10.3171/2022.5.JNS22579. Print 2023 Mar 1.
Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the internal carotid artery (ICA) and secondary formation of collateral vessels. Revascularization surgery is performed in patients with MMD to prevent stroke; however, the pathogenesis of MMD remains unknown. Recently, long noncoding RNAs (lncRNAs) have been found to play a key role in gene regulation and are implicated in various vascular diseases. However, the lncRNA expression profile in MMD lesions has not been investigated. In this study the authors aimed to determine the characteristics of lncRNA expression in MMD lesions.
The authors collected microsamples of the middle cerebral artery (MCA) from patients with MMD (n = 21) and patients with control conditions (n = 11) who underwent neurosurgical treatment. Using microarray experiments, the authors compared the profiles of lncRNA expression in the MCAs of the MMD and control patient groups and identified differentially expressed lncRNAs (fold change > 2, q < 0.05). In addition, the neighboring coding genes, whose transcription can be regulated in cis by the identified differentially expressed lncRNAs, were investigated and Gene Ontology (GO) analysis was applied to predict associated biological functions.
The authors detected 308 differentially expressed lncRNAs (fold change > 2, q < 0.05), including 306 upregulated and 2 downregulated lncRNAs in the MCA from patients with MMD. Regarding the prediction of biological function, GO analyses with possible coding genes whose transcription was regulated in cis by the identified differentially expressed lncRNAs suggested involvement in the antibacterial humoral response, T-cell receptor signaling pathway, positive regulation of cytokine production, and branching involved in blood vessel morphogenesis.
The profile of lncRNA expression in MMD lesions was different from that in the normal cerebral artery, and differentially expressed lncRNAs were identified. This study provides new insights into the pathophysiology of MMD.
烟雾病（MMD）是一种罕见的脑血管疾病，其特征为颈内动脉（ICA）进行性狭窄并继发侧支血管形成。烟雾病患者需进行血管重建手术以预防中风；然而，烟雾病的发病机制仍不清楚。最近，长链非编码RNA（lncRNAs）被发现可在基因调控中发挥关键作用，并与多种血管疾病有关。然而，尚未对烟雾病病变中的lncRNA表达谱进行研究。在本研究中，作者旨在确定烟雾病病变中lncRNA表达的特征。
作者收集了接受神经外科治疗的烟雾病患者（n = 21）和对照患者（n = 11）大脑中动脉（MCA）的微量样本。通过微阵列实验，作者比较了烟雾病患者组和对照患者组MCA中lncRNA的表达谱，并鉴定了差异表达的lncRNAs（倍数变化> 2，q < 0.05）。此外，研究了其转录可由鉴定出的差异表达lncRNAs顺式调控的相邻编码基因，并应用基因本体（GO）分析来预测相关的生物学功能。
作者在烟雾病患者的MCA中检测到308个差异表达的lncRNAs（倍数变化> 2，q < 0.05），其中包括306个上调的lncRNAs和2个下调的lncRNAs。关于生物学功能的预测，对其转录由鉴定出的差异表达lncRNAs顺式调控的可能编码基因进行的GO分析表明，它们参与抗菌体液反应、T细胞受体信号通路、细胞因子产生的正调控以及参与血管形态发生的分支。
烟雾病病变中lncRNA的表达谱与正常脑动脉不同，并鉴定出了差异表达的lncRNAs。本研究为烟雾病的病理生理学提供了新的见解。
