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Peripheral blood monocyte Sirt1 expression is reduced in patients with coronary artery disease

Alexander Breitenstein1, Christophe A Wyss, Remo D Spescha

  • 1Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.

Plos One
|February 6, 2013
PubMed

Insights

Monocytic Sirt1 expression is reduced in patients with coronary artery disease (CAD) and acute coronary syndromes (ACS). This reduction is linked to high-density lipoprotein (HDL) and decreased paraoxonase-1 (PON1) activity.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Immunology

Background:

  • Inflammation is central to atherosclerosis development.
  • Sirtuin 1 (Sirt1) regulates inflammatory transcription factors and has shown protective effects against atherosclerosis in mouse models.
  • The role of Sirt1 in human atherosclerosis requires further investigation.

Purpose of the Study:

  • To investigate the role of Sirt1 in the pathogenesis of atherosclerosis in human subjects.
  • To determine Sirt1 expression levels in monocytes of individuals with varying degrees of coronary artery disease.
  • To explore the influence of high-density lipoprotein (HDL) on Sirt1 expression and its potential link to paraoxonase-1 (PON1) activity.

Main Methods:

  • Analysis of Sirt1 messenger RNA (mRNA) levels in monocytes from 48 male subjects categorized into healthy controls, stable coronary artery disease (CAD), and acute coronary syndromes (ACS) groups.
  • Correlation analysis between Sirt1 expression and high-density lipoprotein (HDL) levels.
  • In vitro experiments involving incubation of THP-1 monocytes with HDL isolated from the study groups to assess HDL's effect on Sirt1 protein expression.
  • Measurement of paraoxonase-1 (PON1) activity in isolated HDL from the different subject groups.

Main Results:

  • Sirt1 gene expression was significantly lower in monocytes from patients with CAD and ACS compared to healthy subjects.
  • HDL levels positively correlated with Sirt1 expression.
  • HDL isolated from healthy subjects demonstrated a greater capacity to stimulate Sirt1 expression in THP-1 monocytes than HDL from CAD and ACS patients.
  • Paraoxonase-1 (PON1) activity was markedly reduced in HDL derived from CAD and ACS patients relative to controls.

Conclusions:

  • Monocytic Sirt1 expression is diminished in individuals with stable CAD and ACS.
  • The observed reduction in Sirt1 expression appears to be dependent on high-density lipoprotein (HDL) functionality.
  • Decreased activity of the HDL-associated enzyme paraoxonase-1 (PON1) may contribute to the impaired Sirt1 regulation in atherosclerosis.
Abstract

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