血管内血流分流后脑动脉瘤的内皮细胞转录调控

IF 3 2区 医学 Q3 ENGINEERING, BIOMEDICAL
Guilherme Barros, Emma Federico, Patrick Fillingham, Pritha Chanana, Naoki Kaneko, Ying Zheng, Louis J. Kim, Michael R. Levitt
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引用次数: 0

摘要

目的:分流支架(FDS)通过促进血栓形成和动脉瘤囊闭塞来治疗脑动脉瘤。然而,在某些情况下需要再次治疗,而治疗结果背后的生物学基础尚不清楚。本研究的目的是了解放置 FDS 后血流动力学的变化如何影响动脉瘤内皮细胞(EC)的活性:方法:建立患者特异性动脉瘤的三维模型,量化EC对FDS置入的反应。计算流体动力学模拟用于确定 FDS 对血液动力学的影响。为每位患者创建了两个完全相同的模型;在其中一个模型中插入了 FDS。从每个模型的动脉瘤穹隆中分离出心肌细胞,并对其进行大量 RNA 测序:结果:为四名患者创建了未治疗和已治疗的配对模型。动脉瘤穹隆 EC 分析显示,在 13909 个总表达基因中,366 个(2.6%)基因在未处理和 FDS 条件下发生了显著变化。对未经处理的模型进行的基因组富集分析表明,富集的基因本体术语与细胞粘附、生长/拉伸活动、细胞骨架组织和钙离子结合有关。在 FDS 模型中,富集的术语与细胞增殖、核糖体活性、RNA 剪接和蛋白质折叠有关:结论:在患者特异性体外三维打印模型中,用 FDS 治疗脑动脉瘤可诱导与动脉瘤血流动力学相关的 EC 基因转录发生显著变化。转录变化与治疗效果之间的关系还需要进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Endothelial Cell Transcription Modulation in Cerebral Aneurysms After Endovascular Flow Diversion

Endothelial Cell Transcription Modulation in Cerebral Aneurysms After Endovascular Flow Diversion

Purpose

Flow diverting stents (FDS) are used to treat cerebral aneurysms, by promoting thrombosis and occlusion of the aneurysm sac. However, retreatment is required in some cases, and the biologic basis behind treatment outcome is not known. The goal of this study was to understand how changes in hemodynamic flow after FDS placement affect aneurysmal endothelial cell (EC) activity.

Methods

Three-dimensional models of patient-specific aneurysms were created to quantify the EC response to FDS placement. Computational fluid dynamic simulations were used to determine the hemodynamic impact of FDS. Two identical models were created for each patient; into one a FDS was inserted. Each model was then populated with human carotid ECs and subjected to patient-specific pulsatile flow for 24 h. ECs were isolated from aneurysm dome from each model and bulk RNA sequencing was performed.

Results

Paired untreated and treated models were created for four patients. Aneurysm dome EC analysis revealed 366 (2.6%) significant gene changes between the untreated and FDS conditions, out of 13909 total expressed genes. Gene set enrichment analysis of the untreated models demonstrated enriched gene ontology terms related to cell adhesion, growth/tensile activity, cytoskeletal organization, and calcium ion binding. In the FDS models, enriched terms were related to cellular proliferation, ribosomal activity, RNA splicing, and protein folding.

Conclusion

Treatment of cerebral aneurysms with FDS induces significant EC gene transcription changes related to aneurysm hemodynamics in patient-specific in vitro 3D-printed models subjected to pulsatile flow. Further investigation is needed into the relationship between transcriptional change and treatment outcome.

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来源期刊
Annals of Biomedical Engineering
Annals of Biomedical Engineering 工程技术-工程:生物医学
CiteScore
7.50
自引率
15.80%
发文量
212
审稿时长
3 months
期刊介绍: Annals of Biomedical Engineering is an official journal of the Biomedical Engineering Society, publishing original articles in the major fields of bioengineering and biomedical engineering. The Annals is an interdisciplinary and international journal with the aim to highlight integrated approaches to the solutions of biological and biomedical problems.
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