CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
PLoS One. 2019 Sep 18;14(9):e0221811. doi: 10.1371/journal.pone.0221811. eCollection 2019.
Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology, sharing many similar clinical symptoms with other vascular disorders. This study aimed to investigate gene dysregulation in peripheral blood of MMD and compare it with other vascular disorders.
Transcriptomic profiles of 12 MMD patients and 8 healthy controls were obtained using RNA sequencing. Differentially expressed genes (DEGs) were identified and several were validated by quantitative real-time PCR in independent samples. Biological pathway enrichment analysis of DEGs and deconvolution of leukocyte subsets in peripheral blood were performed. Expression profiles for other vascular diseases were downloaded from public database and consistent DEGs were calculated. Gene set enrichment analysis (GSEA) was conducted to compare gene dysregulation pattern between MMD and other vascular diseases.
A total of 533 DEGs were identified for MMD. Up-regulated genes were mainly involved in extracellular matrix (ECM) organization, whereas down-regulated genes were primarily associated with inflammatory and immune responses. As for cell populations, significantly increased naïve B cells and naïve CD4 cells as well as obviously decreased resting natural killer cells were observed in peripheral blood of MMD patients. GSEA analysis indicated that only up-regulated genes of ischemic stroke and down-regulated genes of coronary artery disease and myocardial infarction were enriched in up-regulated and down-regulated genes of MMD, respectively.
Dysregulated genes in peripheral blood of MMD mainly played key roles in ECM organization, inflammatory and immune responses. This gene dysregulation pattern was specific compared with other vascular diseases. Besides, naïve B cells, naïve CD4 cells and resting natural killer cells were aberrantly disrupted in peripheral blood of MMD patients. These results will help elucidate the complicated pathogenic mechanism of MMD.
烟雾病（MMD）是一种病因不明的慢性闭塞性脑血管病，与其他血管疾病有许多相似的临床症状。本研究旨在探讨 MMD 患者外周血中的基因失调，并与其他血管疾病进行比较。
采用 RNA 测序技术获取 12 例 MMD 患者和 8 例健康对照者的转录组谱。鉴定差异表达基因（DEGs），并在独立样本中通过定量实时 PCR 验证部分基因。对 DEGs 进行生物通路富集分析，并对外周血中的白细胞亚群进行反卷积分析。从公共数据库中下载其他血管疾病的表达谱，计算一致的 DEGs。进行基因集富集分析（GSEA）比较 MMD 与其他血管疾病之间的基因失调模式。
共鉴定出 533 个与 MMD 相关的 DEGs。上调基因主要参与细胞外基质（ECM）组织，而下调基因主要与炎症和免疫反应有关。对于细胞群体，MMD 患者外周血中幼稚 B 细胞和幼稚 CD4 细胞明显增加，静止自然杀伤细胞明显减少。GSEA 分析表明，只有缺血性卒中的上调基因和冠心病及心肌梗死的下调基因在 MMD 的上调和下调基因中分别富集。
MMD 患者外周血中失调的基因主要参与 ECM 组织、炎症和免疫反应。与其他血管疾病相比，这种基因失调模式具有特异性。此外，MMD 患者外周血中的幼稚 B 细胞、幼稚 CD4 细胞和静止自然杀伤细胞异常失调。这些结果将有助于阐明 MMD 复杂的发病机制。
