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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-45463

Stein, S; Matter, C M (2011). Protective roles of SIRT1 in atherosclerosis. Cell Cycle, 10(4):640-647.

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Abstract

SIRT1 is a NAD (+) -dependent class III histone deacetylase (HDAC) that mediates the effects of caloric restriction on lifespan and metabolic pathways in various organisms. It deacetylates both histone and non-histone proteins, and targets proteins with diverse cellular and tissue functions. In the vasculature of rodent models SIRT1 mediates vasodilatation via eNOS-derived nitric oxide (NO) and scavenging reactive oxygen species (ROS). Recent studies demonstrated further protective roles of SIRT1 in vascular biology and atherosclerosis. In endothelial cells and macrophages SIRT1 has anti-inflammatory functions by downregulating the expression of various pro-inflammatory cytokines by interfering with the NF-kB signaling pathway. Deacetylation of RelA/p65-NF-kB by SIRT1 in macrophages also suppresses the expression of Lox-1, a scavenger receptor for oxidized low-density lipoproteins (oxLDL), thereby preventing macrophage foam cell formation. Moreover, SIRT1 has been shown to regulate the activity of Liver X-receptor (LXR), thereby promoting ABCA1-driven reverse cholesterol transport in plaque macrophages. Finally, SIRT1 suppresses the expression of endothelial tissue factor (coagulation factor III) and hence exerts anti-thrombotic properties. These findings indicate atheroprotective effects of SIRT1 in atherogenesis and highlight the need for translational research from bench-to-bedside. Indeed, SIRT1 activators are available for experimental research and undergo clinical testing. Taken together, these studies suggest SIRT1 activation as a promising therapeutic approach in atherosclerosis. Further studies are necessary to better understand the exact role of SIRT1 in the protagonist cells orchestrating atherogenesis and to identify the specificity, target effects and putative off-target effects of these promising SIRT1 activators.

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51 citations in Web of Science®
55 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:08 Mar 2011 16:11
Last Modified:16 Dec 2013 11:17
Publisher:Landes Bioscience
ISSN:1551-4005
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.4161/cc.10.4.14863
PubMed ID:21293192

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