title: Granulocyte-CSF induced inflammation-associated cardiac thrombosis in iron loading mouse heart and can be attenuated by statin therapy.
abstract: BACKGROUND
  Granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine, was recently used to treat patients of acute myocardial infarction with beneficial effect. However, controversy exists as some patients developed re-stenosis and worsened condition post G-CSF delivery. This study presents a new disease model to study G-CSF induced cardiac thrombosis and delineate its possible mechanism. We used iron loading to mimic condition of chronic cardiac dysfunction and apply G-CSF to mice to test our hypothesis.
  
  
  RESULTS
  Eleven out of fifteen iron and G-CSF treated mice (I+G) showed thrombi formation in the left ventricular chamber with impaired cardiac function. Histological analysis revealed endothelial fibrosis, increased macrophage infiltration and tissue factor expression in the I+G mice hearts. Simvastatin treatment to I+G mice attenuated their cardiac apoptosis, iron deposition, and abrogated thrombus formation by attenuating systemic inflammation and leukocytosis, which was likely due to the activation of pAKT activation. However, thrombosis in I+G mice could not be suppressed by platelet receptor inhibitor, tirofiban.
  
  
  CONCLUSIONS
  Our disease model demonstrated that G-CSF induces cardiac thrombosis through an inflammation-thrombosis interaction and this can be attenuated via statin therapy. Present study provides a mechanism and potential therapy for G-CSF induced cardiac thrombosis.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Wei S
authors.initials: WS
authors.lastname: Lian
authors.forename: Heng
authors.initials: H
authors.lastname: Lin
authors.forename: Winston Tk
authors.initials: WT
authors.lastname: Cheng
authors.forename: Tateki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Ching F
authors.initials: CF
authors.lastname: Cheng
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D005355:Fibrosis; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007501:Iron / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000139:chemically induced* / Q000188:drug therapy*; D019821:Simvastatin / Q000627:therapeutic use; D013927:Thrombosis / Q000139:chemically induced* / Q000188:drug therapy*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016179:Granulocyte Colony-Stimulating Factor; D014443:Tyrosine; D019821:Simvastatin; D007501:Iron; D000077466:Tirofiban