Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan.
Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan.
Peptides. 2019 Jan;111:77-88. doi: 10.1016/j.peptides.2018.10.002. Epub 2018 Oct 21.
Endothelin-1 (ET-1), a 21-amino acid peptide, was initially identified in 1988 as a potent vasoconstrictor and pressor substance isolated from the culture supernatant of porcine aortic endothelial cells. From human genomic DNA analysis, two other family peptides, ET-2 and ET-3, were found. They showed different effects and distribution, suggesting that each peptide may play separate roles in different organs. In the heart, ET-1 also causes positive inotropic and chronotropic responses and hypertrophic activity of the cardiomyocytes. ETs act via activation of two receptor subtypes, ET and ET receptors, both of which are coupled to various GTP-binding proteins depending on cell types. Endogenous ET-1 may be involved in progression of various cardiovascular diseases. ET antagonists are currently used clinically in the treatment for patients with pulmonary hypertension, and are considered to have further target diseases as heart failure, cardiac hypertrophy and other cardiac diseases, renal diseases, systemic hypertension, and cerebral vasospasm.
内皮素-1（ET-1）是一种 21 个氨基酸的肽，最初于 1988 年被鉴定为一种从猪主动脉内皮细胞培养上清液中分离出来的强效血管收缩剂和升压物质。从人类基因组 DNA 分析中，发现了另外两种家族肽，即 ET-2 和 ET-3。它们表现出不同的作用和分布，表明每种肽可能在不同的器官中发挥不同的作用。在心脏中，ET-1 还引起心肌的正性变力和变时反应以及心肌肥厚活性。ET 通过激活两种受体亚型，即 ET 和 ET 受体发挥作用，这两种受体都根据细胞类型与各种 GTP 结合蛋白偶联。内源性 ET-1 可能参与各种心血管疾病的进展。ET 拮抗剂目前在肺动脉高压患者的治疗中临床应用，并被认为有进一步的目标疾病，如心力衰竭、心肌肥厚和其他心脏疾病、肾脏疾病、系统性高血压和脑血管痉挛。
