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

作者：Günaj Rakipovski, Bidda Rolin, Jane Nøhr, Ib Vestergaard Klewe, Klaus Stensgaard Frederiksen, Robert Augustin, Jacob Hecksher‐Sørensen, Camilla Ingvorsen, Joseph Polex-Wolf, Lotte Bjerre Knudsen · 发表于：JACC Basic to Translational Science · 年份：2018 · DOI：10.1016/j.jacbts.2018.09.004 · 被引用次数：510 · 研究领域：Diabetes Treatment and Management、Metabolism, Diabetes, and Cancer、Helicobacter pylori-related gastroenterology studies

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.