The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways

The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways

Summary: The glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients. The mode of action is suggested to occur through modified atherosclerotic progression. In this study, both of the compounds significantly attenuated p...

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Main Authors: Günaj Rakipovski, PhD, Bidda Rolin, DVM, Jane Nøhr, PhD, Ib Klewe, PhD, Klaus S. Frederiksen, PhD, Robert Augustin, PhD, Jacob Hecksher-Sørensen, PhD, Camilla Ingvorsen, PhD, Joseph Polex-Wolf, PhD, Lotte Bjerre Knudsen, DMSc
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:JACC: Basic to Translational Science
Online Access:http://www.sciencedirect.com/science/article/pii/S2452302X18302389
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spelling doaj-2d522d42a8bd4b7390f2d85e3fee3cac2020-11-24T20:58:11ZengElsevierJACC: Basic to Translational Science2452-302X2018-12-0136844857The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory PathwaysGünaj Rakipovski, PhD0Bidda Rolin, DVM1Jane Nøhr, PhD2Ib Klewe, PhD3Klaus S. Frederiksen, PhD4Robert Augustin, PhD5Jacob Hecksher-Sørensen, PhD6Camilla Ingvorsen, PhD7Joseph Polex-Wolf, PhD8Lotte Bjerre Knudsen, DMSc9Global Research, Novo Nordisk A/S, Maaloev, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, Denmark; Biopeople, University of Copenhagen, Copenhagen, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, Denmark; Department of Signal Transduction, Lundbeck, Copenhagen, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, Denmark; Gubra, Hørsholm, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, DenmarkGlobal Research, Novo Nordisk A/S, Maaloev, Denmark; Address for correspondence: Dr. Lotte Bjerre Knudsen, Novo Nordisk, Novo Nordisk Park, DK-2760 Maaloev, Denmark.Summary: The glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients. The mode of action is suggested to occur through modified atherosclerotic progression. In this study, both of the compounds significantly attenuated plaque lesion development in apolipoprotein E-deficient (ApoE−/−) mice and low-density lipoprotein receptor-deficient (LDLr−/−) mice. This attenuation was partly independent of weight and cholesterol lowering. In aortic tissue, exposure to a Western diet alters expression of genes in pathways relevant to the pathogenesis of atherosclerosis, including leukocyte recruitment, leukocyte rolling, adhesion/extravasation, cholesterol metabolism, lipid-mediated signaling, extracellular matrix protein turnover, and plaque hemorrhage. Treatment with semaglutide significantly reversed these changes. These data suggest GLP-1RAs affect atherosclerosis through an anti-inflammatory mechanism. Key Words: atherosclerosis, diabetes, GLP-1, inflammation, obesityhttp://www.sciencedirect.com/science/article/pii/S2452302X18302389
collection DOAJ
language English
format Article
sources DOAJ
author Günaj Rakipovski, PhD
Bidda Rolin, DVM
Jane Nøhr, PhD
Ib Klewe, PhD
Klaus S. Frederiksen, PhD
Robert Augustin, PhD
Jacob Hecksher-Sørensen, PhD
Camilla Ingvorsen, PhD
Joseph Polex-Wolf, PhD
Lotte Bjerre Knudsen, DMSc
spellingShingle Günaj Rakipovski, PhD
Bidda Rolin, DVM
Jane Nøhr, PhD
Ib Klewe, PhD
Klaus S. Frederiksen, PhD
Robert Augustin, PhD
Jacob Hecksher-Sørensen, PhD
Camilla Ingvorsen, PhD
Joseph Polex-Wolf, PhD
Lotte Bjerre Knudsen, DMSc
The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways
JACC: Basic to Translational Science
author_facet Günaj Rakipovski, PhD
Bidda Rolin, DVM
Jane Nøhr, PhD
Ib Klewe, PhD
Klaus S. Frederiksen, PhD
Robert Augustin, PhD
Jacob Hecksher-Sørensen, PhD
Camilla Ingvorsen, PhD
Joseph Polex-Wolf, PhD
Lotte Bjerre Knudsen, DMSc
author_sort Günaj Rakipovski, PhD
title The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways
title_short The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways
title_full The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways
title_fullStr The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways
title_full_unstemmed The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways
title_sort glp-1 analogs liraglutide and semaglutide reduce atherosclerosis in apoe−/− and ldlr−/− mice by a mechanism that includes inflammatory pathways
publisher Elsevier
series JACC: Basic to Translational Science
issn 2452-302X
publishDate 2018-12-01
description Summary: The glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients. The mode of action is suggested to occur through modified atherosclerotic progression. In this study, both of the compounds significantly attenuated plaque lesion development in apolipoprotein E-deficient (ApoE−/−) mice and low-density lipoprotein receptor-deficient (LDLr−/−) mice. This attenuation was partly independent of weight and cholesterol lowering. In aortic tissue, exposure to a Western diet alters expression of genes in pathways relevant to the pathogenesis of atherosclerosis, including leukocyte recruitment, leukocyte rolling, adhesion/extravasation, cholesterol metabolism, lipid-mediated signaling, extracellular matrix protein turnover, and plaque hemorrhage. Treatment with semaglutide significantly reversed these changes. These data suggest GLP-1RAs affect atherosclerosis through an anti-inflammatory mechanism. Key Words: atherosclerosis, diabetes, GLP-1, inflammation, obesity
url http://www.sciencedirect.com/science/article/pii/S2452302X18302389
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