A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE(-/-) mouse model

作者：Gaspari Tracey; Liu HongBin; Welungoda Iresha; Hu Yunshan; Widdop Robert E; Knudsen Lotte B; Simpson Richard W; Dear Anthony E^*

来源：Diabetes and Vascular Disease Research, 2011, 8(2): 117-124.

DOI：10.1177/1479164111404257

• Endothelium
• GLP-1
• incretin
• liraglutide
• NF kappa B

The glucagon like peptide-1 receptor (GLP-1R) agonist liraglutide attenuates induction of plasminogen activator inhibitor type-1 (PAI-1) and vascular adhesion molecule (YAM) expression in human vascular endothelial cells (hVECs) in vitro and may afford protection against endothelial cell dysECD), an early abnormality in diabetic vascular disease. Our study aimed to establish the dependence of the in vitro effects of liraglutide on the GLP-1R and characterise its in vivo effects in a mouse model of ECD. In vitro studies utilised the human vascular endothelial cell line C1 1-STH and enzyme-linked immunosorbent assays (ELISA) for determination of PAI-I and YAM expression. In vivo studies of vascular reactivity and immunohistochemical analysis were performed in the ApoE(-/-) mouse model. In vitro studies demonstrated GLP-1R-dependent liraglutide-mediated inhibition of stimulated PAI-1 and YAM expression. In vivo studies demonstrated significant improvement in endothelial function in liraglutide treated mice, a GLP-1R dependent effect. Liraglutide treatment also increased endothelial nitric oxide synthase (eNOS) and reduced intercellular adhesion molecule-1 (ICAM-1) expression in aortic endothelium, an effect again dependent on the GLP-1R. Together these studies identify in vivo protection, by the GLP-1R agonist liraglutide, against ECD and provide a potential molecular mechanism responsible for these effects.

• 出版日期2011-4