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Mol Biol Rep. 2013 Mar;40(3):2273-9. doi: 10.1007/s11033-012-2290-8. Epub 2012 Nov 28.

GLP-1-dependent and independent effects and molecular mechanisms of a dipeptidyl peptidase 4 inhibitor in vascular endothelial cells.

Author information

1
Eastern Clinical Research Unit, Translational Research Division, Department of Medicine, Australian Centre for Blood Diseases, Monash University, 89 Commercial Rd., Prahran 3181, Melbourne, VIC, Australia.

Erratum in

  • Mol Biol Rep. 2013 Feb;40(2):2059. Y, Hu [corrected to Hu, Yunshan]; Hb, Liu [corrected to Liu, HongBin]; Rw, Simpson [corrected to Simpson, Richard W]; Ae, Dear [corrected to Dear, Anthony E].

Abstract

The potential atheroprotective effects of glucagon-like peptide-1 (GLP-1), long-acting GLP-1 analogues and inhibitors of the enzyme dipeptidyl peptidase 4 (DPP-4) are currently the subject of intense research. Recent evidence suggests the effects of DPP-IV inhibitors, may, in-part, be mediated by GLP-1 independent molecular mechanisms. In this report we demonstrate that treatment of human vascular endothelial cells with the DPP-IV inhibitor sitagliptin inhibited tumour necrosis factor alpha (TNFα) induction of plasminogen activator inhibitor type-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein expression and that this effect was observed to be both GLP-1-dependent and independent. Importantly we identify a molecular mechanism involving sitagliptin-mediated attenuation of TNFα-mediated induction of NFκB and orphan nuclear receptor NUR77 mRNA expression, also able to be reproduced, in part, independent of GLP-1. Taken together these observations may serve to provide a molecular explanation, involving transcriptional regulation of gene expression, for recent in vivo studies suggesting DPP-IV inhibitors may have novel, GLP-1 independent, effects in acting to attenuate endothelial cell dysfunction and atherogenesis.

PMID:
23187735
DOI:
10.1007/s11033-012-2290-8
[Indexed for MEDLINE]

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