Kowalczyk Agata, Kleniewska Paulina, Kolodziejczyk Michal, Skibska Beata, Goraca Anna
Chair of Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland,
Arch Immunol Ther Exp (Warsz). 2015 Feb;63(1):41-52. doi: 10.1007/s00005-014-0310-1. Epub 2014 Oct 7.
Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor, mainly secreted by endothelial cells. It acts through two types of receptors: ETA and ETB. Apart from a vasoconstrictive action, ET-1 causes fibrosis of the vascular cells and stimulates production of reactive oxygen species. It is claimed that ET-1 induces proinflammatory mechanisms, increasing superoxide anion production and cytokine secretion. A recent study has shown that ET-1 is involved in the activation of transcription factors such as NF-κB and expression of proinflammatory cytokines including TNF-α, IL-1, and IL-6. It has been also indicated that during endotoxaemia, the plasma level of ET-1 is increased in various animal species. Some authors indicate a clear correlation between endothelin plasma level and morbidity/mortality rate in septic patients. These pathological effects of ET-1 may be abrogated at least partly by endothelin receptor blockade. ET-1 receptor antagonists may be useful for prevention of various vascular diseases. This review summarises the current knowledge regarding endothelin receptor antagonists and the role of ET-1 in sepsis and inflammation.
内皮素-1（ET-1）是一种强效的内源性血管收缩剂，主要由内皮细胞分泌。它通过两种类型的受体起作用：ETA和ETB。除血管收缩作用外，ET-1还会导致血管细胞纤维化并刺激活性氧的产生。据称，ET-1可诱导促炎机制，增加超氧阴离子的产生和细胞因子的分泌。最近的一项研究表明，ET-1参与转录因子如NF-κB的激活以及促炎细胞因子如TNF-α、IL-1和IL-6的表达。也有研究表明，在内毒素血症期间，各种动物物种的血浆ET-1水平都会升高。一些作者指出，脓毒症患者血浆内皮素水平与发病率/死亡率之间存在明显的相关性。ET-1的这些病理作用至少可以部分通过内皮素受体阻断来消除。ET-1受体拮抗剂可能对预防各种血管疾病有用。这篇综述总结了关于内皮素受体拮抗剂以及ET-1在脓毒症和炎症中的作用的当前知识。
