Pathology and Protein Changes of the Spinal Dural Arteriovenous Fistula Arterial Draining Vein Under Sustained High Vascular Pressure.
Pathology and Protein Changes of the Spinal Dural Arteriovenous Fistula Arterial Draining Vein Under Sustained High Vascular Pressure.
复制标题
持续高血管压力下硬脊膜动静脉瘘动脉引流静脉的病理及蛋白质变化
DOI：
10.3389/fneur.2021.713355
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发表时间：
2021
影响因子：
3.4
通讯作者：
An Q
中科院分区：
文献类型：
--
作者：
Liu P;Shi Y;Li S;Liu Y;Zhou Y;Song Y;Zhu W;An Q
目的：硬脊膜动静脉瘘（SDAVF）是最常见的脊髓血管分流病变。虽然SDAVF引流静脉（SDAVF-DV）的病理变化已经阐明，蛋白质的变化仍然是谜。我们研究了持续高血管压力下SDAVF-DV的病理学和蛋白质变化。方法：将三个SDAVF-DV样本与作为对照的颞浅动脉（STA）和颞浅静脉（STV）样本进行比较。HE染色及Masson染色显示血管结构;免疫组化观察细胞分布、细胞外基质及炎症浸润。无标记的定量蛋白质组学进行，和肽混合物进行分级分离和液相色谱-串联质谱（LC-MS/MS）分析，以确定差异表达的蛋白质。使用基因本体论（GO）、京都基因和基因组百科全书（KEGG）和蛋白质-蛋白质相互作用（PPI）网络对差异表达的蛋白质进行生物信息学分析。结果：H&E和Masson染色显示SDAVF-DV呈动脉样结构。免疫组化显示，SDAVF-DV中vWF+细胞不连续。虽然STV中α-SMA+和AT 1+细胞比SDAVF-DV中更丰富，但SDAVF-DV中piezo-1表达较低。SDAVF-DV显示弹性蛋白、COL I和COL III的不同分布。与对照组相比，SDAVF-DV中COL IV和COL VI减少，而CD 45+细胞和考克斯-1增加。SDAVF-DV和对照组之间未观察到CD 68表达和考克斯-2染色存在差异。与STA相比，SDAVF-DV中有95个蛋白表达上调，303个蛋白表达下调。每个类别中最具差异的GO术语是腺苷酸环化酶调节G蛋白偶联受体信号传导途径、U6 snRNP和SH 3结构域结合。最差异表达的KEGG蛋白途径是粘着斑。与STV相比，SDAVF-DV有158个蛋白表达上调，362个蛋白表达下调。每个类别中最具差异的GO术语是板状伪足组装、U6 snRNP和SH 3结构域结合;最具差异表达的KEGG蛋白途径是扩张型心肌病。PPI分析显示PPI在前300种蛋白质中。结论：SDAVF-DV在持续高血压下表现出特异性的病理变化和蛋白表达变化。本研究结果为从蛋白质水平深入了解SDAVF形成的发病机制提供了科学依据，也为进一步探讨SDAVF的病理生理机制提供了科学依据。
Object: Spinal dural arteriovenous fistula (SDAVF) is the most common spinal vascular shunt lesion. Although pathological changes in the SDAVF draining vein (SDAVF-DV) have been elucidated, protein changes remain enigmatic. We investigated the pathology and protein changes in the SDAVF-DV under sustained high vascular pressure. Methods: Three SDAVF-DV samples were compared with superficial temporal artery (STA) and superficial temporal vein (STV) samples as controls. Vascular structure was revealed by hematoxylin and eosin (H&E) and Masson staining; and cell distribution, extracellular matrix, and inflammation infiltration were observed by immunohistochemistry. Label-free quantitative proteomics was performed, and the peptide mixture was fractionated and analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins. Bioinformatics analysis of the differentially expressed proteins was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) networks. Results: H&E and Masson staining showed an artery-like structure of the SDAVF-DV. Immunostaining showed that vWF+ cells were not continuous in the SDAVF-DV. Although α-SMA+ and AT1+ cells were more abundant in the STV than in the SDAVF-DV, piezo-1 expression was lower in the SDAVF-DV. The SDAVF-DV showed different distributions of elastin, COL I, and COL III. COL IV and COL VI were decreased in the SDAVF-DV, while CD45+ cells and COX-1 were increased compared with those in the controls. No differences in CD68 expression and COX-2 staining were observed between the SDAVF-DV and controls. Compared with the STA, 95 proteins were upregulated and 303 proteins were downregulated in the SDAVF-DV. The most differential GO terms in each category were the adenylate cyclase-modulating G protein-coupled receptor signaling pathway, U6 snRNP, and SH3 domain binding. The most differentially expressed KEGG protein pathway was focal adhesion. Compared with the STV, the SDAVF-DV had 158 upregulated proteins and 362 downregulated proteins. The most differential GO terms in each category were lamellipodium assembly, U6 snRNP, and SH3 domain binding; and the most differentially expressed KEGG protein pathway was dilated cardiomyopathy. PPI analysis revealed PPIs among the top 300 proteins. Conclusions: The SDAVF-DV exhibits specific pathology and protein expression changes under sustained high vascular pressure. The results of the present study provide insights into the pathogenesis of SDAVF formation at the protein level as well as a scientific foundation for further exploration of the pathophysiological mechanism of the SDAVF.
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影响因子：
2.8
作者：
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通讯作者：
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