title: Clopidogrel attenuates atheroma formation and induces a stable plaque phenotype in apolipoprotein E knockout mice.
abstract: OBJECTIVE
  Clopidogrel is a widely used anti-thrombotic for the prevention of stent thrombosis and cardiovascular events in patients with coronary atherosclerosis. Clopidogrel has been shown to exhibit anti-inflammatory effects that are related to the attenuated activation of platelets. Atherosclerosis is a complex process in which the immune system and the endothelium appear to play a prominent role. Herein, we tested the hypothesis that clopidogrel will influence plaque size and composition in the atherosclerosis prone apolipoprotein E knockout (apoE KO) mouse model.
  
  
  RESULTS
  Eight week old mice were fed daily with either PBS, 1 mg or 2 mg of clopidogrel for 10 weeks. Plaque size was evaluated in the aortic sinus and cellular and humoral responses were studied as well as splenic and bone marrow endothelial progenitors by FACS. Treatment with either 1 mg and 2 mg of clopidogrel significantly reduced plaque size and augmented its stability by increasing atheromatous fibrous area. Whereas antigen specific oxLDL immune response was not influenced by clopidogrel feeding, the number of atheroprotective regulatory CD4+CD25+ T cells was significantly increased. Moreover, clopidogrel treatment resulted in a prominent rise in splenic but not bone marrow derived Sca-1+/flk-1+ endothelial progenitors.
  
  
  CONCLUSIONS
  Clopidogrel significantly reduces atheroma burden and stabilizes aortic sinus plaques in apoE KO mice. These effects may partially be mediated by upregulation of the regulatory T cell pool and splenic endothelial progenitor cells. These findings may expand the potential applications of clopidogrel in human subjects.
authors.affiliation: The Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Afek
authors.forename: Evgeny
authors.initials: E
authors.lastname: Kogan
authors.forename: Sofia
authors.initials: S
authors.lastname: Maysel-Auslender
authors.forename: Adi
authors.initials: A
authors.lastname: Mor
authors.forename: Ehud
authors.initials: E
authors.lastname: Regev
authors.forename: Ardon
authors.initials: A
authors.lastname: Rubinstein
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
authors.forename: Jacob
authors.initials: J
authors.lastname: George