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GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotox...

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Autores principales: Helmstädter, Johanna, Keppeler, Karin, Aust, Franziska, Küster, Leonie, Frenis, Katie, Filippou, Konstantina, Vujacic-Mirski, Ksenija, Tsohataridis, Simeon, Kalinovic, Sanela, Kröller-Schön, Swenja, Oelze, Matthias, Bosmann, Markus, Münzel, Thomas, Daiber, Andreas, Steven, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388926/
https://www.ncbi.nlm.nih.gov/pubmed/34439423
http://dx.doi.org/10.3390/antiox10081175
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author Helmstädter, Johanna
Keppeler, Karin
Aust, Franziska
Küster, Leonie
Frenis, Katie
Filippou, Konstantina
Vujacic-Mirski, Ksenija
Tsohataridis, Simeon
Kalinovic, Sanela
Kröller-Schön, Swenja
Oelze, Matthias
Bosmann, Markus
Münzel, Thomas
Daiber, Andreas
Steven, Sebastian
author_facet Helmstädter, Johanna
Keppeler, Karin
Aust, Franziska
Küster, Leonie
Frenis, Katie
Filippou, Konstantina
Vujacic-Mirski, Ksenija
Tsohataridis, Simeon
Kalinovic, Sanela
Kröller-Schön, Swenja
Oelze, Matthias
Bosmann, Markus
Münzel, Thomas
Daiber, Andreas
Steven, Sebastian
author_sort Helmstädter, Johanna
collection PubMed
description Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.
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spelling pubmed-83889262021-08-27 GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation Helmstädter, Johanna Keppeler, Karin Aust, Franziska Küster, Leonie Frenis, Katie Filippou, Konstantina Vujacic-Mirski, Ksenija Tsohataridis, Simeon Kalinovic, Sanela Kröller-Schön, Swenja Oelze, Matthias Bosmann, Markus Münzel, Thomas Daiber, Andreas Steven, Sebastian Antioxidants (Basel) Article Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis. MDPI 2021-07-23 /pmc/articles/PMC8388926/ /pubmed/34439423 http://dx.doi.org/10.3390/antiox10081175 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Helmstädter, Johanna
Keppeler, Karin
Aust, Franziska
Küster, Leonie
Frenis, Katie
Filippou, Konstantina
Vujacic-Mirski, Ksenija
Tsohataridis, Simeon
Kalinovic, Sanela
Kröller-Schön, Swenja
Oelze, Matthias
Bosmann, Markus
Münzel, Thomas
Daiber, Andreas
Steven, Sebastian
GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation
title GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation
title_full GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation
title_fullStr GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation
title_full_unstemmed GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation
title_short GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation
title_sort glp-1 analog liraglutide improves vascular function in polymicrobial sepsis by reduction of oxidative stress and inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388926/
https://www.ncbi.nlm.nih.gov/pubmed/34439423
http://dx.doi.org/10.3390/antiox10081175
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