Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress

IF 3.4 3区 医学 Q2 HEMATOLOGY
Allaura A. Cox, Christopher James Ng
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引用次数: 0

Abstract

Background

Endothelial cell (EC) heterogeneity is an emerging area of research in EC biology. Vein, artery, and microvascular ECs have been shown to have heterogeneity in gene expression and function, termed “vascular-type” heterogeneity in this report. In addition to this innate heterogeneity, we hypothesized that different vascular-type ECs would also demonstrate heterogeneity in their response to shear stress.

Objectives

We interrogated whether vascular-type ECs would demonstrate variations in transcriptional expression patterns under shear stress.

Methods

Human umbilical vein ECs, human pulmonary arterial ECs, and human microvascular ECs were commercially purchased and subjected to 0, 1, 4, and 10 dynes/cm2 of laminar shear stress. After shear stress exposure, cellular alignment was analyzed, and RNA was extracted and evaluated via bulk RNA sequencing.

Results

All ECs demonstrated significant changes in alignment under shear stress. Shear stress significantly affected the transcriptomes of ECs, resulting in differential expression of genes and pathways. While several genes were differentially expressed by all 3 vascular EC types (44.2%), most differentially expressed genes were limited to 1 or 2 of the vascular types. Hemostatic and thrombotic genes were found to have differential expression patterns under conditions of shear stress, and von Willebrand factor demonstrated a pattern of vascular-type heterogeneity in response to shear stress.

Conclusion

Shear stress causes changes in cellular alignment and transcriptional patterns in ECs that are dependent upon underlying vascular type. Therefore, endothelial vascular-type heterogeneity can regulate response to shear stress, especially in hemostatic and thrombotic gene expression.
血管类型的异质性与内皮细胞在剪切应力下的差异基因表达谱有关
内皮细胞异质性是内皮生物学研究的一个新兴领域。静脉、动脉和微血管内皮细胞在基因表达和功能上具有异质性,在本报告中称为“血管型”异质性。除了这种先天的异质性,我们假设不同的血管型内皮细胞在对剪切应力的反应中也表现出异质性。目的探讨血管型内皮细胞在剪切胁迫下是否表现出转录表达模式的变化。方法选择市购的人脐静脉内皮细胞、人肺动脉内皮细胞和人微血管内皮细胞,分别承受0、1、4、10达因/cm2的层流剪切应力。在剪切应力暴露后,分析细胞排列,提取RNA并通过大量RNA测序进行评估。结果所有内皮细胞在剪切应力作用下均表现出明显的取向变化。剪切应力显著影响ECs的转录组,导致基因和通路的差异表达。虽然有几个基因在3种血管型EC中均有差异表达(44.2%),但大多数差异表达基因仅限于1或2种血管型。止血和凝血基因在剪切应力条件下具有不同的表达模式,血管性血友病因子在剪切应力下表现出血管类型的异质性。结论剪切应力导致内皮细胞的细胞排列和转录模式的改变,这种改变依赖于潜在的血管类型。因此,内皮血管类型的异质性可以调节对剪切应力的反应,特别是在止血和血栓基因表达方面。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.60
自引率
13.00%
发文量
212
审稿时长
7 weeks
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