{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:04:45Z","timestamp":1793109885194,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG STE2528\/2-1"],"award-info":[{"award-number":["DFG STE2528\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BO3482\/3-3"],"award-info":[{"award-number":["BO3482\/3-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BO3482\/4-1"],"award-info":[{"award-number":["BO3482\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["BMBF 01EO1003"],"award-info":[{"award-number":["BMBF 01EO1003"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HL141513"],"award-info":[{"award-number":["1R01HL141513"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HL139641"],"award-info":[{"award-number":["1R01HL139641"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AI153613"],"award-info":[{"award-number":["1R01AI153613"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1UL1TR001430"],"award-info":[{"award-number":["1UL1TR001430"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/antiox10081175","type":"journal-article","created":{"date-parts":[[2021,7,25]],"date-time":"2021-07-25T22:06:21Z","timestamp":1627250781000},"page":"1175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation"],"prefix":"10.3390","volume":"10","author":[{"given":"Johanna","family":"Helmst\u00e4dter","sequence":"first","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Keppeler","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Aust","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"K\u00fcster","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-0882","authenticated-orcid":false,"given":"Katie","family":"Frenis","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Filippou","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-4209","authenticated-orcid":false,"given":"Ksenija","family":"Vujacic-Mirski","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeon","family":"Tsohataridis","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-2425","authenticated-orcid":false,"given":"Sanela","family":"Kalinovic","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swenja","family":"Kr\u00f6ller-Sch\u00f6n","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Oelze","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2773-1033","authenticated-orcid":false,"given":"Markus","family":"Bosmann","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131 Mainz, Germany"},{"name":"Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-4150","authenticated-orcid":false,"given":"Thomas","family":"M\u00fcnzel","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2769-0094","authenticated-orcid":false,"given":"Andreas","family":"Daiber","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5332-9294","authenticated-orcid":false,"given":"Sebastian","family":"Steven","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology 1\u2013Molecular Cardiology, University Medical Center, 55131 Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","article-title":"Biology of incretins: Glp-1 and gip","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Helmstadter, J., Keppeler, K., Kuster, L., Munzel, T., Daiber, A., and Steven, S. 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