Liraglutide dictates macrophage phenotype in apolipoprotein E null mice during early atherosclerosis

• DOI: 10.1186/s12933-017-0626-3
• Publication Date: 2017-11-06T12:35:57Z
• Authors: Robyn Bruen; Sean Curley; Sarina Kajani; Daniel Crean; Marcella E. O’Reilly; Margaret B. Lucitt; Catherine G. Godson; Fiona C. McGillic...; Orina Belton
• Keywords: Apolipoprotein E; M2 Macrophage; Monocyte

Macrophages play a pivotal role in atherosclerotic plaque development. Recent evidence has suggested the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, can attenuate pro-inflammatory responses macrophages. We hypothesized that liraglutide could limit atherosclerosis progression vivo via modulation of inflammatory response. Human THP-1 macrophages and bone marrow-derived macrophages, from both wild-type C57BL/6 (WT) apolipoprotein E null mice (ApoE−/−) were used to investigate effect on response vitro. In parallel, ApoE−/− fed high-fat (60% calories fat) high-cholesterol (1%) diet for 8 weeks induce disease with/without daily 300 μg/kg administration final 6 weeks. analysed MΦ1 MΦ2 macrophage markers by Western blotting, RT-qPCR, ELISA flow cytometry. Atherosclerotic lesions aortae en face staining monocyte populations marrow derived cells Liraglutide decreased lesion formation coincident with reduction increased anti-inflammatory monocyte/macrophage vivo. IL-1beta MΦ0 WT induced significant increase surface marker mannose Significant total development was found once treatment mice. Interestingly, inhibited at iliac bifurcation suggesting it retards initiation disease. These results corresponded attenuated (CCR7, IL-6 TNF-alpha), augmented cell (Arg-1, IL-10 CD163) finally MΦ1-like monocytes cells. This data supports therapeutic as an atheroprotective agent modulating fate towards pro-resolving