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PLoS By Category | Recent PLoS Articles
Cardiovascular Disorders

Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells
Published: Friday, January 28, 2011
Author: Caterina Mammi et al.

by Caterina Mammi, Donatella Pastore, Marco F. Lombardo, Francesca Ferrelli, Massimiliano Caprio, Claudia Consoli, Manfredi Tesauro, Lucia Gatta, Massimo Fini, Massimo Federici, Paolo Sbraccia, Giulia Donadel, Alfonso Bellia, Giuseppe M. Rosano, Andrea Fabbri, Davide Lauro

Background

The efficacy of Phosphodiesterase 5 (PDE5) inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e. sildenafil, may increase the expression of nitric oxide synthase (NOS) proteins in the heart and cardiomyocytes. In this study we analyzed the effect of sildenafil on endothelial cells in insulin resistance conditions in vitro.

Methodology/Principal Findings

Human umbilical vein endothelial cells (HUVECs) were treated with insulin in presence of glucose 30 mM (HG) and glucosamine 10 mM (Gluc-N) with or without sildenafil. Insulin increased the expression of PDE5 and eNOS mRNA assayed by Real time-PCR. Cytofluorimetric analysis showed that sildenafil significantly increased NO production in basal condition. This effect was partially inhibited by the PI3K inhibitor LY 294002 and completely inhibited by the NOS inhibitor L-NAME. Akt-1 and eNOS activation was reduced in conditions mimicking insulin resistance and completely restored by sildenafil treatment. Conversely sildenafil treatment can counteract this noxious effect by increasing NO production through eNOS activation and reducing oxidative stress induced by hyperglycaemia and glucosamine.

Conclusions/Significance

These data indicate that sildenafil might improve NOS activity of endothelial cells in insulin resistance conditions and suggest the potential therapeutic use of sildenafil for improving vascular function in diabetic patients.

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