Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability

Abstract Septic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid...

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Autores principales:	Takeshi Tanaka, Masahiko Mori, Motohiro Sekino, Ushio Higashijima, Masahiro Takaki, Yoshiro Yamashita, Satoshi Kakiuchi, Masato Tashiro, Konosuke Morimoto, Osamu Tasaki, Koichi Izumikawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a138fd391aa49a0b38ffb1150730c77
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spelling	oai:doaj.org-article:8a138fd391aa49a0b38ffb1150730c772021-12-02T15:22:57ZImpact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability10.1038/s41598-021-93649-z2045-2322https://doaj.org/article/8a138fd391aa49a0b38ffb1150730c772021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93649-zhttps://doaj.org/toc/2045-2322Abstract Septic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid (5-HIAA) on septic shock as a novel biomarker. Plasma 5-HIAA levels and disease severity indices were obtained from 47 patients with sepsis. The association between 5-HIAA levels and severity indices was analyzed. Permeability upon serotonin stimulation was determined using human pulmonary microvascular ECs. 5-HIAA were significantly higher in septic shock patients than in patients without shock or healthy controls (p = 0.004). These elevated levels were correlated with severity indexes (SOFA score [p < 0.001], APACHE II [p < 0.001], and PaO2:FiO2 [p = 0.02]), and longitudinally associated with worse clinical outcomes (mechanical ventilation duration [p = 0.009] and ICU duration [p = 0.01]). In the experiment, serotonin increased the permeability of ECs, which was inhibited by the ROCK inhibitor (p < 0.001). Serotonin increases vascular permeability of ECs via ROCK signaling. This suggests a novel mechanism by which serotonin disrupts endothelial barriers via ROCK signaling and causes the pathogenesis of septic shock with a vascular leak. Serotonin serves as a novel biomarker of vascular permeability.Takeshi TanakaMasahiko MoriMotohiro SekinoUshio HigashijimaMasahiro TakakiYoshiro YamashitaSatoshi KakiuchiMasato TashiroKonosuke MorimotoOsamu TasakiKoichi IzumikawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takeshi Tanaka Masahiko Mori Motohiro Sekino Ushio Higashijima Masahiro Takaki Yoshiro Yamashita Satoshi Kakiuchi Masato Tashiro Konosuke Morimoto Osamu Tasaki Koichi Izumikawa Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
description	Abstract Septic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid (5-HIAA) on septic shock as a novel biomarker. Plasma 5-HIAA levels and disease severity indices were obtained from 47 patients with sepsis. The association between 5-HIAA levels and severity indices was analyzed. Permeability upon serotonin stimulation was determined using human pulmonary microvascular ECs. 5-HIAA were significantly higher in septic shock patients than in patients without shock or healthy controls (p = 0.004). These elevated levels were correlated with severity indexes (SOFA score [p < 0.001], APACHE II [p < 0.001], and PaO2:FiO2 [p = 0.02]), and longitudinally associated with worse clinical outcomes (mechanical ventilation duration [p = 0.009] and ICU duration [p = 0.01]). In the experiment, serotonin increased the permeability of ECs, which was inhibited by the ROCK inhibitor (p < 0.001). Serotonin increases vascular permeability of ECs via ROCK signaling. This suggests a novel mechanism by which serotonin disrupts endothelial barriers via ROCK signaling and causes the pathogenesis of septic shock with a vascular leak. Serotonin serves as a novel biomarker of vascular permeability.
format	article
author	Takeshi Tanaka Masahiko Mori Motohiro Sekino Ushio Higashijima Masahiro Takaki Yoshiro Yamashita Satoshi Kakiuchi Masato Tashiro Konosuke Morimoto Osamu Tasaki Koichi Izumikawa
author_facet	Takeshi Tanaka Masahiko Mori Motohiro Sekino Ushio Higashijima Masahiro Takaki Yoshiro Yamashita Satoshi Kakiuchi Masato Tashiro Konosuke Morimoto Osamu Tasaki Koichi Izumikawa
author_sort	Takeshi Tanaka
title	Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
title_short	Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
title_full	Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
title_fullStr	Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
title_full_unstemmed	Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
title_sort	impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8a138fd391aa49a0b38ffb1150730c77
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Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability

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