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

[Display omitted] •The GLP-1RAs liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients.•In ApoE−/− mice and LDLr−/− mice, liraglutide and semaglutide treatment significantly attenuated plaque lesion development, in part independently of body weight and cholesterol lowerin...

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Veröffentlicht in:JACC. Basic to translational science Jg. 3; H. 6; S. 844 - 857
Hauptverfasser: Rakipovski, Günaj, Rolin, Bidda, Nøhr, Jane, Klewe, Ib, Frederiksen, Klaus S., Augustin, Robert, Hecksher-Sørensen, Jacob, Ingvorsen, Camilla, Polex-Wolf, Joseph, Knudsen, Lotte Bjerre
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 01.12.2018
Elsevier
Schlagworte:
atherosclerosis
Cardiovascular
diabetes
GLP-1
inflammation
obesity
PRECLINICAL RESEARCH
atherosclerosis
CD163
GLP-1
IL
RNA
GLP
NASH
OPN
TNF
WD
LPS
IFN
MMP
inflammation
LDL
diabetes
obesity
TIMP
cluster of differentiation 163 molecule
ribonucleic acid
nonalcoholic steatohepatitis
tissue inhibitor of metalloproteinases
glucagon-like peptide
interleukin
osteopontin
interferon
low-density lipoprotein
tumor necrosis factor
matrix metalloproteinase
lipopolysaccharide
Western diet
IFN, interferon
CD163, cluster of differentiation 163 molecule
RNA, ribonucleic acid
TNF, tumor necrosis factor
OPN, osteopontin
NASH, nonalcoholic steatohepatitis
IL, interleukin
LPS, lipopolysaccharide
WD, Western diet
TIMP, tissue inhibitor of metalloproteinases
LDL, low-density lipoprotein
MMP, matrix metalloproteinase
GLP, glucagon-like peptide
ISSN:2452-302X, 2452-302X
Online-Zugang:Volltext
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Zusammenfassung:[Display omitted] •The GLP-1RAs liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients.•In ApoE−/− mice and LDLr−/− mice, liraglutide and semaglutide treatment significantly attenuated plaque lesion development, in part independently of body weight and cholesterol lowering.•Semaglutide decreased levels of plasma markers of systemic inflammation in an acute inflammation model (lipopolysaccharide), and transcriptomic analysis of aortic atherosclerotic tissue revealed that multiple inflammatory pathways were down-regulated by semaglutide. 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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2452-302X
2452-302X
DOI:10.1016/j.jacbts.2018.09.004