edoc

SIRT1 reduces endothelial activation without affecting vascular function in ApoE-/- mice

Stein, Sokrates and Schäfer, Nicola and Breitenstein, Alexander and Besler, Christian and Winnik, Stephan and Lohmann, Christine and Heinrich, Kathrin and Brokopp, Chad E. and Handschin, Christoph and Landmesser, Ulf and Tanner, Felix C. and Lüscher, Thomas F. and Matter, Christian M.. (2010) SIRT1 reduces endothelial activation without affecting vascular function in ApoE-/- mice. Aging, Vol. 2, H. 6. pp. 353-360.

[img]
Preview
PDF - Published Version
Available under License CC BY (Attribution).

1859Kb

Official URL: http://edoc.unibas.ch/dok/A5842426

Downloads: Statistics Overview

Abstract

Excessive production of reactive oxygen species (ROS) contributes to progression of atherosclerosis, at least in part by causing endothelial dysfunction and inflammatory activation. The class III histone deacetylase SIRT1 has been implicated in extension of lifespan. In the vasculature,SIRT1 gain-of-function using SIRT1 overexpression or activation has been shown to improve endothelial function in mice and rats via stimulation of endothelial nitric oxide (NO) synthase (eNOS). However, the effects of SIRT1 loss-of-function on the endothelium in atherosclerosis remain to be characterized. Thus, we have investigated the endothelial effects of decreased endogenous SIRT1 in hypercholesterolemic ApoE-/- mice. We observed no difference in endothelial relaxation and eNOS (Ser1177) phosphorylation between 20-week old male atherosclerotic ApoE-/- SIRT1+/- and ApoE-/- SIRT1+/+ mice. However, SIRT1 prevented endothelial superoxide production, inhibited NF-kappaB signaling, and diminished expression of adhesion molecules. Treatment of young hypercholesterolemic ApoE-/- SIRT1+/- mice with lipopolysaccharide to boost NF-kappaB signaling led to a more pronounced endothelial expression of ICAM-1 and VCAM-1 as compared to ApoE-/- SIRT1+/+ mice. In conclusion, endogenous SIRT1 diminishes endothelial activation in ApoE-/- mice, but does not affect endothelium-dependent vasodilatation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Related URLs:
Identification Number:
Last Modified:31 Dec 2015 10:49
Deposited On:08 Jun 2012 06:51

Repository Staff Only: item control page