Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 2273 - 2279 |
| Number of pages | 7 |
| Journal | Molecular Biology Reports |
| Volume | 40 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2013 |
Cite this
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GLP-1-dependent and independent effects and molecular mechanisms of a dipeptidyl peptidase 4 inhibitor in vascular endothelial cells. / Hu, Yunshan; Liu, Hong Bin; Simpson, Richard; Dear, Anthony Edwin.
In: Molecular Biology Reports, Vol. 40, No. 3, 2013, p. 2273 - 2279.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - GLP-1-dependent and independent effects and molecular mechanisms of a dipeptidyl peptidase 4 inhibitor in vascular endothelial cells
AU - Hu, Yunshan
AU - Liu, Hong Bin
AU - Simpson, Richard
AU - Dear, Anthony Edwin
PY - 2013
Y1 - 2013
N2 - 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 (TNFa) 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 TNFa-mediated induction of NF?B 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.
AB - 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 (TNFa) 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 TNFa-mediated induction of NF?B 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.
UR - http://link.springer.com/content/pdf/10.1007%2Fs11033-012-2290-8.pdf
U2 - 10.1007/s11033-012-2290-8
DO - 10.1007/s11033-012-2290-8
M3 - Article
VL - 40
SP - 2273
EP - 2279
JO - Molecular Biology Reports
JF - Molecular Biology Reports
SN - 0301-4851
IS - 3
ER -