title: Expression of the aging gene p66Shc is increased in peripheral blood monocytes of patients with acute coronary syndrome but not with stable coronary artery disease.
abstract: OBJECTIVE
  The interplay between oxidative stress and inflammation is crucial in the pathogenesis of atherosclerosis. The adaptor protein p66Shc is implicated in atherogenesis and oxidative stress related responses in animal models of diseases. However, its role in humans remains to be defined. In this study, we hypothesized that expression of p66Shc increases in peripheral blood monocytes of patients affected by acute coronary syndromes (ACS).
  
  
  METHODS
  Male subjects aged 59±4 (mean±SD) years admitted for cardiac catheterization were subdivided in three groups: (a) no local stenosis for the control group, (b) at least one stenosis ≥75% in either left, circumflex or right coronary artery for the coronary artery disease (CAD) group or (c) ST-elevation/non-ST-elevation myocardial infarction for the ACS group. Monocytes were isolated from whole blood and p66Shc RNA levels were determined by quantitative real time PCR.
  
  
  RESULTS
  p66Shc RNA levels were increased in ACS patients as compared to CAD (p=0.007) and controls (p=0.0249). Furthermore, malondialdehyde (MDA) and C-reactive protein (CRP) were increased in plasma of ACS patients. Levels of MDA correlated positively to p66Shc (r=0.376, p=0.01). Our data demonstrate increased p66Shc levels in monocytes of ACS but not CAD patients.
  
  
  CONCLUSIONS
  This study suggests an involvement of p66Shc in the transition of a stable CAD to an ACS patient. p66Shc was associated with states of increased oxidative stress. Further work is needed to understand whether p66Shc may represent a possible pharmacological target or whether it represents an interesting novel biomarker.
authors.affiliation: Cardiovascular Center, Cardiology, University Hospital of Zurich, Switzerland.
authors.forename: Fabian C
authors.initials: FC
authors.lastname: Franzeck
authors.forename: Danielle
authors.initials: D
authors.lastname: Hof
authors.forename: Remo D
authors.initials: RD
authors.lastname: Spescha
authors.forename: Matthias
authors.initials: M
authors.lastname: Hasun
authors.forename: Alexander
authors.initials: A
authors.lastname: Akhmedov
authors.forename: Jan
authors.initials: J
authors.lastname: Steffel
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cosentino
authors.forename: Felix C
authors.initials: FC
authors.lastname: Tanner
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.forename: Willibald
authors.initials: W
authors.lastname: Maier
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Christophe A
authors.initials: CA
authors.lastname: Wyss
authors.forename: Giovanni G
authors.initials: GG
authors.lastname: Camici
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry*; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013557:Switzerland; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D008315:Malondialdehyde