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血管基因表达的分子分析

Molecular analysis of vascular gene expression.

作者信息

Van der Ent Martijn A, Svilar David, Cleuren Audrey C A

机构信息

Department of Microbiology and Immunology University of Michigan Ann Arbor Michigan USA.

Department of Pediatrics University of Michigan Ann Arbor Michigan USA.

出版信息

Res Pract Thromb Haemost. 2022 May 19;6(4):e12718. doi: 10.1002/rth2.12718. eCollection 2022 May.

Abstract

A State of the Art lecture entitled "Molecular Analysis of Vascular Gene Expression" was presented at the ISTH Congress in 2021. Endothelial cells (ECs) form a critical interface between the blood and underlying tissue environment, serving as a reactive barrier to maintain tissue homeostasis. ECs play an important role in not only coagulation, but also in the response to inflammation by connecting these two processes in the host defense against pathogens. Furthermore, ECs tailor their behavior to the needs of the microenvironment in which they reside, resulting in a broad display of EC phenotypes. While this heterogeneity has been acknowledged for decades, the contributing molecular mechanisms have only recently started to emerge due to technological advances. These include high-throughput sequencing combined with methods to isolate ECs directly from their native tissue environment, as well as sequencing samples at a high cellular resolution. In addition, the newest technologies simultaneously quantitate and visualize a multitude of RNA transcripts directly in tissue sections, thus providing spatial information. Understanding how ECs function in (patho)physiological conditions is crucial to develop new therapeutics as many diseases can directly affect the endothelium. Of particular relevance for thrombotic disorders, EC dysfunction can lead to a procoagulant, proinflammatory phenotype with increased vascular permeability that can result in coagulopathy and tissue damage, as seen in a number of infectious diseases, including sepsis and coronavirus disease 2019. In light of the current pandemic, we will summarize relevant new data on the latter topic presented during the 2021 ISTH Congress.

摘要

一场题为“血管基因表达的分子分析”的前沿讲座于2021年在国际血栓与止血学会(ISTH)大会上发表。内皮细胞(ECs)在血液与下层组织环境之间形成关键界面,作为维持组织稳态的反应屏障。内皮细胞不仅在凝血中起重要作用,还通过在宿主抵御病原体的防御过程中将这两个过程联系起来,在炎症反应中发挥重要作用。此外,内皮细胞根据其所处微环境的需求调整自身行为,从而呈现出广泛的内皮细胞表型。虽然这种异质性已被认识数十年,但由于技术进步,其相关分子机制直到最近才开始显现。这些技术包括高通量测序以及直接从其天然组织环境中分离内皮细胞的方法,还有在高细胞分辨率下对样本进行测序。此外,最新技术可同时在组织切片中直接对多种RNA转录本进行定量和可视化,从而提供空间信息。了解内皮细胞在(病理)生理条件下的功能对于开发新疗法至关重要,因为许多疾病可直接影响内皮。对于血栓性疾病而言尤其相关,内皮功能障碍可导致促凝血、促炎表型,血管通透性增加,进而可导致凝血病和组织损伤,如在包括脓毒症和2019冠状病毒病在内的多种传染病中所见。鉴于当前的大流行情况,我们将总结在2021年ISTH大会期间提出的关于后一主题的相关新数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adfd/9118339/cdb53be81026/RTH2-6-e12718-g002.jpg

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