Endothelial cell malfunction in unruptured intracranial aneurysm lesions revealed using a 3D-casted mold
Endothelial cell malfunction in unruptured intracranial aneurysm lesions revealed using a 3D-casted mold
复制标题
使用 3D 铸造模具揭示未破裂颅内动脉瘤病变中的内皮细胞功能障碍
DOI：
10.1093/jnen/nlac104
复制
发表时间：
2022
影响因子：
3.2
通讯作者：
Aoki Tomohiro
中科院分区：
文献类型：
--
作者：
Ono Isao;Abekura Yu;Kawashima Akitsugu;Oka Mieko;Okada Akihiro;Hara Shintaro;Miyamoto Susumu;Kataoka Hiroharu;Ishii Akira;Yamamoto Kimiko;Aoki Tomohiro
颅内动脉瘤（IA）是破坏性蛛网膜下腔出血的主要原因。其特征在于颅内动脉壁中的慢性炎症过程，其由血流动力学力负荷触发和改变。由于IA病变形态复杂，因此在病变的每个部分中原位加载在内皮细胞上的血流条件变化很大。我们创建了一个三维铸造模具的人类未破裂的IA病变和培养内皮细胞在这个模型上，然后灌注培养基模拟生理流动条件。然后分析IA病变的每个部分中的内皮细胞的基因表达谱。全面的基因表达谱分析显示，相似的基因表达模式，在内皮细胞从每一个部分的IA病变，但基因本体分析显示，内皮细胞功能障碍内IA病变。组织学检查，电子显微镜和免疫组化分析表明，内IA病变的内皮细胞受损和功能障碍。因此，我们的研究结果揭示了血管内皮细胞功能障碍的IA病变，并提供了新的见解IA的发病机制。
Intracranial aneurysms (IA) are major causes of devastating subarachnoid hemorrhages. They are characterized by a chronic inflammatory process in the intracranial arterial walls triggered and modified by hemodynamic force loading. Because IA lesion morphology is complex, the blood flow conditions loaded on endothelial cells in each portion of the lesion in situ vary greatly. We created a 3D-casted mold of the human unruptured IA lesion and cultured endothelial cells on this model; it was then perfused with culture media to model physiological flow conditions. Gene expression profiles of endothelial cells in each part of the IA lesion were then analyzed. Comprehensive gene expression profile analysis revealed similar gene expression patterns in endothelial cells from each part of the IA lesion but gene ontology analysis revealed endothelial cell malfunction within the IA lesion. Histopathological examination, electron microscopy, and immunohistochemical analysis indicated that endothelial cells within IA lesions are damaged and dysfunctional. Thus, our findings reveal endothelial cell malfunction in IA lesions and provided new insights into IA pathogenesis.