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内皮素-1 陷阱作为一种有潜力的治疗工具:从糖尿病到更远?

Endothelin-1 traps as a potential therapeutic tool: from diabetes to beyond?

机构信息

Accelerate Cambridge, Judge Business School, University of Cambridge, Cambridge, UK.

Wapiti Medical, Milbank, SD, USA.

出版信息

Drug Discov Today. 2019 Sep;24(9):1937-1942. doi: 10.1016/j.drudis.2019.07.008. Epub 2019 Aug 5.

Abstract

There is substantial research on the vasoactive peptide endothelin (ET)-1 in physiology, as well as in pathology. In fact, pathologically elevated levels of ET-1 have been found in several disease states, such as various cardiovascular diseases, different cancers, some neurodegenerative disorders, as well as in diabetes. Here, we describe and discuss ET-1, its importance in different diseases, and the potential therapeutic effects of ET-traps in the treatment of these diseases. Previous in vitro and in vivo research (in the diabetes disease space) demonstrated that ET-traps potently and significantly prevent the induction of different markers of diabetes-related pathology. This included induction of extracellular matrix (ECM) proteins (collagen 4α1 and fibronectin), which are pathologically elevated in diabetes. The ET-traps prevented induction of these and brought a significant return to non-diabetic levels. We also discuss the merits of using ET-traps over the currently used endothelin receptor antagonists (ERAs) and previously used therapeutic antibodies.

摘要

在生理学和病理学方面,有大量关于血管活性肽内皮素(ET)-1 的研究。事实上,在几种疾病状态下,如各种心血管疾病、不同类型的癌症、一些神经退行性疾病以及糖尿病中,都发现 ET-1 水平病理性升高。在这里,我们描述并讨论了 ET-1 及其在不同疾病中的重要性,以及 ET 陷阱在治疗这些疾病中的潜在治疗效果。先前的体外和体内研究(在糖尿病领域)表明,ET 陷阱能够强有力地显著预防诱导与糖尿病相关病理学的不同标志物。这包括诱导细胞外基质(ECM)蛋白(胶原 4α1 和纤维连接蛋白)的产生,这些蛋白在糖尿病中病理性升高。ET 陷阱阻止了这些标志物的诱导,并使它们显著恢复到非糖尿病水平。我们还讨论了使用 ET 陷阱而不是目前使用的内皮素受体拮抗剂(ERAs)和以前使用的治疗性抗体的优点。

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