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H Liu, Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
A Dear, Australian Centre for Blood Diseases, Monash University, Melbourne, 3181, Australia
L Knudsen, Novo Nordisk A/S, Malov, Denmark
R Simpson, Diabetes and Endocrinology, Box Hill Hospital, Melbourne, Australia

Correspondence: Anthony Dear, Email: anthony.dear{at}med.monash.edu.au

Abstract

Glucagon-Like Peptide-1 (GLP-1) administration attenuates endothelial cell dysfunction in diabetic patients and inhibits tumour necrosis factor alpha (TNF)-mediated plasminogen activator inhibitor type-1 (PAI-1) induction in human vascular endothelial cells. The short half life of GLP-1 mediated via degradation by the enzyme dipeptidyl peptidase 4 (DPP-IV) mandates clinical use of long-acting GLP-1 analogues. The effects of a long-acting GLP-1 analogue on PAI-1 and vascular adhesion molecule expression in vascular endothelial cells is unknown.

In this report we demonstrate for the first time that treatment with liraglutide, a long-acting GLP-1 analogue, inhibited TNF or hyperglycemia-mediated induction of PAI-1, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein expression in a human vascular endothelial cell line. In addition treatment attenuated TNF or hyperglycemia-mediated induction of the orphan nuclear receptor Nur77 mRNA expression. Taken together, these observations indicate that liraglutide inhibits TNF or glucose-mediated induction of PAI-1 and vascular adhesion molecule expression and this effect may involve the modulation of Nur77. These effects suggest that liraglutide may potentially improve the endothelial cell dysfunction associated with premature atherosclerosis identified in type 2 diabetic patients.

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