title: Peripheral blood monocyte Sirt1 expression is reduced in patients with coronary artery disease.
abstract: BACKGROUND
  Inflammation plays a key role in atherosclerosis. Sirt1 regulates transcription factors involved in inflammatory processes and blunts atherosclerosis in mice. However, its role in humans remains to be defined. This study was therefore designed to investigate the role of Sirt1 in the development of atherosclerosis.
  
  
  RESULTS
  48 male subjects admitted for cardiac catheterization were subdivided into healthy subjects, patients with stable coronary artery disease (CAD), and with acute coronary syndromes (ACS). Monocytes were isolated and Sirt1 mRNA levels were determined. Sirt1 gene expression was higher in healthy subjects as compared to patients with CAD or ACS (P<0.05), respectively. Interestingly, HDL levels correlated positively with Sirt1 expression. Thus, HDL from the three groups was isolated and incubated with THP-1 monocytes to determine the effects of HDL on Sirt1 protein in controlled experimental conditions. HDL from healthy subjects stimulated Sirt1 expression in THP-1 monocytes to a higher degree than HDL from CAD and ACS patients (P<0.05). Paraoxonase-1 (PON-1), a HDL-associated enzyme, showed a reduced activity in HDL isolated from CAD and ACS patients as compared to the controls (P<0.001).
  
  
  CONCLUSIONS
  Monocytic Sirt1 expression is reduced in patients with stable CAD and ACS. Experiments on THP-1 monocytes suggest that this effect is HDL-dependent and is mediated by a reduced activity of HDL-associated enzyme PON1.
authors: Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.
authors: Alexander
authors: A
authors: Breitenstein
authors: Christophe A
authors: CA
authors: Wyss
authors: Remo D
authors: RD
authors: Spescha
authors: Fabian C
authors: FC
authors: Franzeck
authors: Danielle
authors: D
authors: Hof
authors: Meliana
authors: M
authors: Riwanto
authors: Matthias
authors: M
authors: Hasun
authors: Alexander
authors: A
authors: Akhmedov
authors: Arnold
authors: A
authors: von Eckardstein
authors: Willibald
authors: W
authors: Maier
authors: Ulf
authors: U
authors: Landmesser
authors: Thomas F
authors: TF
authors: Lüscher
authors: Giovanni G
authors: GG
authors: Camici
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000503:physiopathology; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D056564:Sirtuin 1 / Q000097:blood* / Q000235:genetics
chemical_list: D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase; C447939:SIRT1 protein, human; D056564:Sirtuin 1
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