Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease.
Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease.
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DOI：
10.1038/s41598-021-81282-9
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发表时间：
2021-01-15
影响因子：
4.6
通讯作者：
Kitagawa H
中科院分区：
文献类型：
--
作者：
Matsuo M;Nadanaka S;Soga M;Sugiyama T;Serigano S;Shimano K;Ichinose F;Nakamura T;Maeda T;Houkin K;Era T;Kitagawa H
烟雾病（MMD）的特征是颈内动脉末端部分的进行性双侧狭窄变化。尽管RNF213被确定为MMD的易感基因，但确切的发病机制仍不清楚。对 MMD 患者尸检标本的免疫组织化学分析显示，MMD 闭塞性病变的增厚内膜中透明质酸和硫酸软骨素 (CS) 明显积聚。透明质酸合酶 2 在增厚内膜的内皮祖细胞中强烈表达。此外，MMD 病变在内皮细胞中显示出极少的 CS 和透明质酸染色，而对照内皮细胞则显示出两者均呈阳性染色。源自MMD的内皮细胞和对照诱导多能干细胞的糖胺聚糖显示MMD中CS的量减少，尤其是硫酸化CS的量减少。计算流体动力学模型显示，颈内动脉末端部分的壁剪切应力值最高，这是MMD的易发区域。由于内皮周围细胞外基质在保护、细胞粘附和迁移中发挥重要作用，MMD 中内皮周围基质的改变可能导致内皮细胞对壁剪切应力的脆弱性。入侵的内皮祖细胞修复内皮损伤，会在内膜中产生过量的透明质酸和CS，导致血管狭窄。
Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. Although RNF213 was identified as a susceptibility gene for MMD, the exact pathogenesis remains unknown. Immunohistochemical analysis of autopsy specimens from a patient with MMD revealed marked accumulation of hyaluronan and chondroitin sulfate (CS) in the thickened intima of occlusive lesions of MMD. Hyaluronan synthase 2 was strongly expressed in endothelial progenitor cells in the thickened intima. Furthermore, MMD lesions showed minimal staining for CS and hyaluronan in the endothelium, in contrast to control endothelium showing positive staining for both. Glycosaminoglycans of endothelial cells derived from MMD and control induced pluripotent stem cells demonstrated a decreased amount of CS, especially sulfated CS, in MMD. A computational fluid dynamics model showed highest wall shear stress values in the terminal portion of the internal carotid artery, which is the predisposing region in MMD. Because the peri-endothelial extracellular matrix plays an important role in protection, cell adhesion and migration, an altered peri-endothelial matrix in MMD may contribute to endothelial vulnerability to wall shear stress. Invading endothelial progenitor cells repairing endothelial injury would produce excessive hyaluronan and CS in the intima, and cause vascular stenosis.
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影响因子：
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通讯作者：
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