title: Effects of direct infusion of bone marrow-derived progenitor cells and indirect mobilization of hematopoietic progenitor cells on atherosclerotic plaque and inflammatory process in atherosclerosis.
abstract: BACKGROUND
  We sought to investigate the effects of lin-/sca+ cells, endothelial progenitor cells (EPCs) and granulocyte colony-stimulating factor (G-CSF) administration on atherosclerotic plaque progression.
  
  
  METHODS
  Apolipoprotein E-deficient (apoE(-/-)) mice were splenectomized and treated with high-cholesterol diet for 6 weeks in order to induce atherosclerotic plaque development. Bone marrow-derived Lin-/sca-1+ cells were isolated and further cultured to early growth endothelial progenitor cells (EPCs). Mice were divided in four groups (n=10/group) and received two intravenous injections of 5×10(5) cells (lin-/sca-1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 μg/kg/day) for 7 days or normal saline. The same interventions were administered to animals, which had undergone unilateral hind-limb ischemia. Effects on inflammatory parameters, lesion severity, and atherosclerotic plaque area size were assessed.
  
  
  RESULTS
  The administration of both G-CSF and progenitor cells significantly decreased the levels of IL-6, 6 weeks after the initiation of treatment. Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area percentage 22.94%±3.68, p=0.001), by lin-/sca-1+ (23.27%±5.98, p=0.002) and cultured EPCs (23.16±4.86%, p=0.002) compared to control (32.75%±7.05). In the atherosclerotic mice that underwent limb ischemia, the atherosclerotic plaque area, was not significantly different between the treatment groups cultured EPCs-treated mice and the control group (p=NS, for all).
  
  
  CONCLUSIONS
  Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells decreased plaque progression and levels of inflammatory molecules in a murine model of atherosclerosis. Treatment with G-CSF, lin-/sca-1+, or EPCs may exert beneficial effects on vascular inflammation and atherosclerotic plaque progression. However, the effects are diminished in an ischemic setting.
authors: 1st Cardiology Unit, Athens University Medical School, Greece. Electronic address: drtousoulis@hotmail.com.
authors: Dimitris
authors: D
authors: Tousoulis
authors: Alexandros
authors: A
authors: Briasoulis
authors: Georgia
authors: G
authors: Vogiatzi
authors: Aggeliki
authors: A
authors: Valatsou
authors: Polina
authors: P
authors: Kourkouti
authors: Alkistis
authors: A
authors: Pantopoulou
authors: Nikolaos
authors: N
authors: Papageorgiou
authors: Despina
authors: D
authors: Perrea
authors: Christodoulos
authors: C
authors: Stefanadis
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000473:pathology / Q000601:surgery*; D050197:Atherosclerosis / Q000150:complications / Q000473:pathology / Q000601:surgery*; D002452:Cell Count; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D036502:Infusions, Intralesional; D051379:Mice; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D013234:Stem Cells; D016896:Treatment Outcome
keywords: Atherosclerotic plaque; Inflammation; Ischemia; Progenitor cells