The role of endothelin-1 and new therapeutic approaches in sepsis and septic shock

Year 2015, Volume: 5 Issue: 3, 178 - 190, 01.10.2015

Demet Sinem Güden Meryem Temiz Bahar Tunçtan Seyhan Şahan Fırat

Abstract

As a systemic inflammatory response to infection, sepsis describes a complex clinical syndrome that results in progressively advance stage, probably evoke septic shock, multiple organ dysfunction syndrome and ultimately cause to death. Sepsis is markedly enhanced by proinflammatory cytokines that can trigger a systemic inflammatory cascade mediated by chemokines, vasoactive amines, complement and coagulation system as well as reactive oxygen species (ROS). In 1988, endothelin (ET)-1 was identified as a vasoactive amine from endothelium which has a 21 amino acid peptide. It has been demonstrated with the experimental and clinical studies that endothelin acts as an important role in sepsis and septic shock pathogenesis. Moreover, endothelin receptor antagonists have been studied as novel therapeutic target for treatment of sepsis and septic shock and according to these studies beneficial results have been obtained . Mitogen-activated protein kinase signal transduction pathway is stimulated by ET-1 which activates a variety of downstream molecules; it is believed that ET-1could play an important role in the development of sepsis, septic shock, and multiple organ dysfunction syndrome by events that can cause increased reactive oxygen species (ROS) production, inflammation, endothelial dysfunction, abnormal vascular tonus, and vascular remodelling.

Keywords

Endothelin-1, sepsis, septic shock, inflammation

Sepsis ve septik şok patojenezinde endotelin-1’in rolü ve tedavide yeni yaklaşımlar

Abstract

Vücuda giren patojene karşı gelişen sistemik enflamatuvar yanıt olarak adlandırılan sepsis, septik şok, çoklu organ yetmezliği ve ölümle sonuçlanabilmektedir. Sistemik enflamatuvar yanıtı tetikleyebilen artmış proenflamatuvar sitokin düzeyleriyle birlikte kemokinler, koagülasyon ve kompleman sistemleri ile vazoaktif aminler de sepsis patojenezinde yer almaktadır. Endotelin (ET)-1, 1988 yılında vazoaktif amin olarak damar endotelinden izole edilmiş olup 21 zincirli amino asit zincirine sahip bir peptitdir. (ET)-1’in sepsis ve septik şok gelişimindeki rolü deneysel ve klinik çalışmalarda gösterilmiş olup, reseptör antagonistleri sepsis tedavisinde denenmiş ve yararlı sonuçlar sağlamıştır. ET-1’in mitojenle etkinleştirilen protein kinaz sinyal ileti yolunu uyararak etkinleştirdiği downstream sinyal molekülleri aracılığıyla reaktif oksijen türlerinin üretiminde artış, enflamasyon gelişimi, endotelyal işlevde bozulma, anormal damar gerimi ve damarlarda yeniden modellenme gibi olaylara yol açarak sepsis, septik şok ve çoklu organ yetmezliği gelişiminde önemli rolü olabileceği düşünülmektedir.

Keywords

Endotelin-1, sepsis, septik şok, enflamasyon

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