The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE-/- and LDLr-/- Mice by a Mechanism That Includes Inflammatory Pathways.
JACC Basic Transl Sci
; 3(6): 844-857, 2018 Dec.
Article
em En
| MEDLINE
| ID: mdl-30623143
ABSTRACT
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.
CD163, cluster of differentiation 163 molecule; GLP, glucagon-like peptide; GLP-1; IFN, interferon; IL, interleukin; LDL, low-density lipoprotein; LPS, lipopolysaccharide; MMP, matrix metalloproteinase; NASH, nonalcoholic steatohepatitis; OPN, osteopontin; RNA, ribonucleic acid; TIMP, tissue inhibitor of metalloproteinases; TNF, tumor necrosis factor; WD, Western diet; atherosclerosis; diabetes; inflammation; obesity
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Bases de dados:
MEDLINE
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En
Revista:
JACC Basic Transl Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Dinamarca