PMID- 23259556
OWN - NLM
STAT- MEDLINE
DCOM- 20130703
LR  - 20191027
IS  - 1875-6212 (Electronic)
IS  - 1570-1611 (Linking)
VI  - 10
IP  - 6
DP  - 2012 Nov
TI  - SIRT1 - an anti-inflammatory pathway at the crossroads between metabolic disease 
      and atherosclerosis.
PG  - 693-6
AB  - Atherosclerosis is a chronic inflammatory disease that is based on the 
      interaction between inflammatory cell subsets and specific cells in the arterial 
      wall. SIRT1 deacetylates histone and non-histone proteins and has been implicated 
      in protective effects of caloric restriction on lifespan and metabolic pathways 
      in yeast, nematodes, and mice. In the vasculature of rodents, SIRT1 mediates 
      vasodilatation through the release of endothelial nitric oxide synthase-derived 
      nitric oxide and scavenges reactive oxygen species. Using a genetic 
      loss-of-function approach, SIRT1 has been shown to interfere with crucial steps 
      of endothelial activation and atherogenesis by suppressing NFkappaB signaling: 
      Partial SIRT1 deletion in ApoE-/- mice prevented expression of endothelial 
      adhesion molecules thereby hampering the extravasation of circulating monocytes. 
      In monocyte-derived macrophages SIRT1 deletion reduced the expression of the 
      scavenger receptor lectin-like oxidized low-density lipoprotein receptor 1 
      (Lox-1) resulting in reduced foam cell formation and atherosclerosis. Moreover, 
      it was reported that SIRT1 regulates the activity of liver X-receptor, thereby 
      promoting ABCA1-driven reverse cholesterol transport in plaque-resident 
      macrophages slowing foam cell formation. Finally, SIRT1 suppressed the expression 
      of endothelial tissue factor, and thus exerted anti-thrombotic properties during 
      induced carotid thrombosis in mice. These findings indicate protective effects of 
      SIRT1 in atherogenesis and thrombosis at an experimental level and highlight the 
      opportunity to translate this concept from bench to bedside. Indeed, SIRT1 
      activators are available and have been shown to exert beneficial effects at the 
      preclinical level in obesity and type 2 diabetes mellitus (T2DM). SIRT1 
      activators are currently being evaluated in phase II clinical trials in patients 
      with T2DM. The concept of SIRT1 activation appears a promising strategy for novel 
      therapeutic approaches in patients with atherothrombosis.
FAU - Winnik, Stephan
AU  - Winnik S
AD  - Cardiovascular Research, Institute of Physiology, University of Zurich and 
      Cardiology, Cardiovascular Center, University Hospital Zurich, 
      Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
FAU - Stein, Sokrates
AU  - Stein S
FAU - Matter, Christian M
AU  - Matter CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Vasc Pharmacol
JT  - Current vascular pharmacology
JID - 101157208
RN  - 0 (Enzyme Activators)
RN  - 0 (Inflammation Mediators)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/blood/drug therapy/*enzymology/immunology/physiopathology
MH  - Cholesterol/metabolism
MH  - Endothelium, Vascular/enzymology/physiopathology
MH  - Enzyme Activation
MH  - Enzyme Activators/therapeutic use
MH  - Hemostasis
MH  - Humans
MH  - Inflammation/blood/drug therapy/*enzymology/immunology/physiopathology
MH  - Inflammation Mediators/metabolism
MH  - Metabolic Diseases/blood/drug therapy/*enzymology/immunology/physiopathology
MH  - *Signal Transduction
MH  - Sirtuin 1/antagonists & inhibitors/*metabolism
EDAT- 2012/12/25 06:00
MHDA- 2013/07/05 06:00
CRDT- 2012/12/25 06:00
PHST- 2012/12/25 06:00 [entrez]
PHST- 2012/12/25 06:00 [pubmed]
PHST- 2013/07/05 06:00 [medline]
AID - CVP-10-6-693 [pii]
AID - 10.2174/157016112803520756 [doi]
PST - ppublish
SO  - Curr Vasc Pharmacol. 2012 Nov;10(6):693-6. doi: 10.2174/157016112803520756.