Regulation of Cerebral Vascular Function by Sirtuin 1
Article first published online: 24 APR 2012
© 2012 John Wiley & Sons Ltd
Volume 19, Issue 4, pages 336–342, May 2012
How to Cite
TAJBAKHSH, N. and SOKOYA, E. M. (2012), Regulation of Cerebral Vascular Function by Sirtuin 1. Microcirculation, 19: 336–342. doi: 10.1111/j.1549-8719.2012.00167.x
- Issue published online: 24 APR 2012
- Article first published online: 24 APR 2012
- Accepted manuscript online: 8 FEB 2012 05:25AM EST
- Received 10 January 2012; accepted 31 January 2012.
- middle cerebral artery;
- nitric oxide;
- sirtuin 1
Please cite this paper as: Tajbakhsh N, Sokoya EM. Regulation of cerebral vascular function by sirtuin 1. Microcirculation 19: 336–342, 2012.
Objective: Endothelial dysfunction, associated with reduced nitric oxide bioavailability and oxidative stress, is a common feature of vascular-related diseases. Sirtuin 1 (SIRT1) is a protein deacetylase that has been shown to target endothelial nitric oxide synthase in large arteries and is protective during oxidative stress. However, within resistance-sized vessels, the expression and functional effects of SIRT1 remain unknown.
Methods: Immunoblotting and immunohistochemistry were used to determine SIRT1 expression and localization in cultured brain endothelial cells and intact rat middle cerebral artery. The influence of SIRT1 on vascular function was then studied in intact middle cerebral arteries using pressure myography.
Results: We report for the first time that SIRT1 is expressed in the resistance-sized vessels in the brain and is present in both the endothelium and smooth muscle. Pharmacological inhibition of SIRT1 demonstrated reduced endothelium-dependent dilation mediated by nitric oxide. However, endothelium-independent dilations were comparable in the presence and absence of SIRT1 block.
Conclusions: Our results support a role for SIRT1 in endothelium-dependent relaxation in the cerebral vasculature and reveal a potential for SIRT1 as a therapeutic target in vascular-related diseases by restoring endothelial function.