TY - JOUR

T1 - Liraglutide treatment improves endothelial function in the Ldlr-/- mouse model of atherosclerosis, and affects genes involved in vascular remodelling and inflammation

AU - Bjørnholm, Katrine Dahl

AU - Skovsted, Gry Freja

AU - Mitgaard-Thomsen, Anne

AU - Rakipovski, Günaj

AU - Tveden-Nyborg, Pernille

AU - Lykkesfeldt, Jens

AU - Povlsen, Gro Klitgaard

N1 - This article is protected by copyright. All rights reserved.

PY - 2021

Y1 - 2021

N2 - Recent clinical intervention studies have shown that the GLP1 analogue liraglutide lowers cardiovascular risk, but the underlying mechanism has not yet been fully elucidated. This study investigated effects of liraglutide on endothelial function in the Ldlr-/- mouse model. Mice (n=12/group) were fed western diet or chow for 12 weeks followed by four weeks of treatment with liraglutide (1mg/kg/day) or vehicle subcutaneously. Weight loss, blood lipid content, plaque burden, vasomotor function of the aorta, and gene expression pattern in aorta and brachiocephalic artery were monitored. Liraglutide treatment significantly induced weight loss (p<0.0001), decreased blood triglycerides (p<0.0001), and total cholesterol (p<0.0001) in western diet-fed mice but did not decrease plaque burden. Liraglutide also improved endothelium-mediated dilation of the distal thoracis aorta (p= 0.0067), but it did not affect phenylephrine or sodium nitroprusside responses. Fluidigm analyses of 96 genes showed significantly altered expression of seven genes related to inflammation, vascular smooth muscle cells and extracellular matrix composition in liraglutide-treated animals. We conclude that treatment with liraglutide decreased endothelial dysfunction, and that this could be linked to decreased inflammation or regulation of vascular remodelling.

AB - Recent clinical intervention studies have shown that the GLP1 analogue liraglutide lowers cardiovascular risk, but the underlying mechanism has not yet been fully elucidated. This study investigated effects of liraglutide on endothelial function in the Ldlr-/- mouse model. Mice (n=12/group) were fed western diet or chow for 12 weeks followed by four weeks of treatment with liraglutide (1mg/kg/day) or vehicle subcutaneously. Weight loss, blood lipid content, plaque burden, vasomotor function of the aorta, and gene expression pattern in aorta and brachiocephalic artery were monitored. Liraglutide treatment significantly induced weight loss (p<0.0001), decreased blood triglycerides (p<0.0001), and total cholesterol (p<0.0001) in western diet-fed mice but did not decrease plaque burden. Liraglutide also improved endothelium-mediated dilation of the distal thoracis aorta (p= 0.0067), but it did not affect phenylephrine or sodium nitroprusside responses. Fluidigm analyses of 96 genes showed significantly altered expression of seven genes related to inflammation, vascular smooth muscle cells and extracellular matrix composition in liraglutide-treated animals. We conclude that treatment with liraglutide decreased endothelial dysfunction, and that this could be linked to decreased inflammation or regulation of vascular remodelling.

U2 - 10.1111/bcpt.13486

DO - 10.1111/bcpt.13486

M3 - Journal article

C2 - 32896073

VL - 128

SP - 103

EP - 114

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 1

ER -