[HTML][HTML] Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells
G Aragonès, P Saavedra, M Heras, A Cabré… - Cardiovascular …, 2012 - Springer
Cardiovascular diabetology, 2012•Springer
Background Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma
levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this
work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production
by endothelial cells in vitro. Methods In human umbilical vascular endothelial cells
(HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric
oxide synthase (eNOS) expression and activation and on NO production. We also explored …
levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this
work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production
by endothelial cells in vitro. Methods In human umbilical vascular endothelial cells
(HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric
oxide synthase (eNOS) expression and activation and on NO production. We also explored …
Background
Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro.
Methods
In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation and on NO production. We also explored the impact of exogenous FABP4 on the insulin-signalling pathway (insulin receptor substrate 1 (IRS1) and Akt).
Results
We found that eNOS expression and activation and NO production are significantly inhibited by exogenous FABP4 in HUVECs. FABP4 induced an alteration of the insulin-mediated eNOS pathway by inhibiting IRS1 and Akt activation. These results suggest that FABP4 induces endothelial dysfunction by inhibiting the activation of the insulin-signalling pathway resulting in decreased eNOS activation and NO production.
Conclusion
These findings provide a mechanistic linkage between FABP4 and impaired endothelial function in diabetes, which leads to an increased cardiovascular risk.
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