1. The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways
- Author
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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, and Lotte Bjerre Knudsen, DMSc
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
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
- Published
- 2018
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