ResearchIn-Press PreviewEndocrinology Open Access | 10.1172/jci.insight.153732
1Department of Medicine, LTRI Mt. Sinai Hospital, Toronto, Canada
2Department of Surgery, University of Michigan, Ann Arbor, United States of America
Find articles by McLean, B. in: JCI | PubMed | Google Scholar
1Department of Medicine, LTRI Mt. Sinai Hospital, Toronto, Canada
2Department of Surgery, University of Michigan, Ann Arbor, United States of America
Find articles by Wong, C. in: JCI | PubMed | Google Scholar |
1Department of Medicine, LTRI Mt. Sinai Hospital, Toronto, Canada
2Department of Surgery, University of Michigan, Ann Arbor, United States of America
Find articles by Kaur, K. in: JCI | PubMed | Google Scholar
1Department of Medicine, LTRI Mt. Sinai Hospital, Toronto, Canada
2Department of Surgery, University of Michigan, Ann Arbor, United States of America
Find articles by Seeley, R. in: JCI | PubMed | Google Scholar
1Department of Medicine, LTRI Mt. Sinai Hospital, Toronto, Canada
2Department of Surgery, University of Michigan, Ann Arbor, United States of America
Find articles by Drucker, D. in: JCI | PubMed | Google Scholar |
Published October 21, 2021 - More info
Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat diabetes and obesity and reduce rates of major cardiovascular events such as stroke and myocardial infarction. Nevertheless, the identity of GLP-1R-expressing cell types mediating the cardiovascular benefits of GLP-1RA remains incompletely characterized. Herein, we investigated the importance of murine Glp1r expression within endothelial and hematopoietic cells. Mice with targeted inactivation of the Glp1r in Tie2+ cells exhibited reduced levels of Glp1r mRNA transcripts in aorta, liver, spleen, blood and gut. Glp1r expression in bone marrow cells was very low, and not further reduced in Glp1rTie2-/- mice. The GLP-1RA semaglutide reduced the development of atherosclerosis induced by viral PCSK9 expression in both Glp1rTie2+/+ and Glp1rTie2-/- mice. Hepatic Glp1r mRNA transcripts were reduced in Glp1rTie2-/- mice and liver Glp1r expression was localized to γδ T cells. Moreover, semaglutide reduced hepatic Tnf, Abcg1, Tgfb1, Cd3g, Ccl2, and Il2 expression, triglyceride content and collagen accumulation in high fat high cholesterol (HFHC) diet-fed Glp1rTie2+/+ but not Glp1rTie2-/- mice. Collectively, these findings demonstrate that Tie2+ endothelial or hematopoietic cell GLP-1Rs are dispensable for the anti-atherogenic actions of GLP-1RA, whereas Tie2-targeted GLP-1R+ cells are required for a subset of the anti-inflammatory actions of semaglutide in the liver.