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Article

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

1
Center for Cardiology, Department of Cardiology 1–Molecular Cardiology, University Medical Center, 55131 Mainz, Germany
2
Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131 Mainz, Germany
3
Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
4
German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Langenbeckstr. 1, 55131 Mainz, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Victoria Cachofeiro
Antioxidants 2021, 10(8), 1175; https://doi.org/10.3390/antiox10081175
Received: 29 June 2021 / Revised: 20 July 2021 / Accepted: 21 July 2021 / Published: 23 July 2021
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. View Full-Text
Keywords: glucagon-like peptide-1 (GLP-1); incretins; liraglutide; peritoneal and polymicrobial sepsis; cecal ligation and puncture (CLP); endothelial dysfunction; oxidative stress; vascular inflammation glucagon-like peptide-1 (GLP-1); incretins; liraglutide; peritoneal and polymicrobial sepsis; cecal ligation and puncture (CLP); endothelial dysfunction; oxidative stress; vascular inflammation
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MDPI and ACS Style

Helmstädter, J.; Keppeler, K.; Aust, F.; Küster, L.; Frenis, K.; Filippou, K.; Vujacic-Mirski, K.; Tsohataridis, S.; Kalinovic, S.; Kröller-Schön, S.; Oelze, M.; Bosmann, M.; Münzel, T.; Daiber, A.; Steven, S. GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation. Antioxidants 2021, 10, 1175. https://doi.org/10.3390/antiox10081175

AMA Style

Helmstädter J, Keppeler K, Aust F, Küster L, Frenis K, Filippou K, Vujacic-Mirski K, Tsohataridis S, Kalinovic S, Kröller-Schön S, Oelze M, Bosmann M, Münzel T, Daiber A, Steven S. GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation. Antioxidants. 2021; 10(8):1175. https://doi.org/10.3390/antiox10081175

Chicago/Turabian Style

Helmstädter, Johanna, Karin Keppeler, Franziska Aust, Leonie Küster, Katie Frenis, Konstantina Filippou, Ksenija Vujacic-Mirski, Simeon Tsohataridis, Sanela Kalinovic, Swenja Kröller-Schön, Matthias Oelze, Markus Bosmann, Thomas Münzel, Andreas Daiber, and Sebastian Steven. 2021. "GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation" Antioxidants 10, no. 8: 1175. https://doi.org/10.3390/antiox10081175

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