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

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Rakipovski G, Rolin B, Nohr J, Klewe I, Frederiksen KS, Augustin R, Hecksher-Sorensen J, Ingvorsen C, Polex-Wolf J, Knudsen LB

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. 2018 Nov 21;3(6):844-857. doi: 10.1016/j.jacbts.2018.09.004. eCollection 2018 Dec.

PubMed ID
30623143 [ View in PubMed
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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.

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