Abstract 13209: Inhibition of Atherosclerosis Progression and Improvement of Proinflammatory Markers by Administration of Bone Marrow-Derived Endothelial Progenitor Cells in ApoE Knockout Mice
Background: The effects of direct infusion or indirect mobilization of progenitor cells on atherosclerotic plaque development and progression is not clear. We sought to investigate the effects of lin-/sca+ cells, endothelial progenitor cells and G-CSF administration on the progression of atherosclerosis.
Methods: Apolipoprotein E-deficient (apoE-/-) mice were splenectomized and treated withhigh-cholesterol diet for 5 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 5x105 cells (lin-/sca-1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100mcg/kg/day) for 7 days or normal saline. Effects on inflammatory parameters, lesion severity, atherosclerotic and macrophage area size were assessed.
Results: The administration of both G-CSF and progenitor cells significantly decreased the levels of sICAM-1, sVCAM-1, sE-Selectin, and IL-6, 6 weeks after the initiation of treatment. The effects of all treatments on the levels of pro-inflammatory molecules and oxidative stress parameters 7 days post-treatment were not significant. Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area percentage 22.94%±3.68, P=0.001), lin-/sca-1+ (23.27%±5.98, P=0.002) and cultured EPCs (23.16±4.86%,P=0.002). 80% of the lesions in the control group were severe lesions in comparison to 50% in the G-CSF group (p< 0.05), 46% in the lin-/sca-1+ group (p< 0.05) and 56% in the EPC group (p<0.05) G-CSF, lin-/sca-1+ and EPCs reduced macrophage area (-45%, p< 0.05; -35%, p< 0.05;-48%, p< 0.05, respectively).
Conclusions: Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells significantly inhibited atherosclerosis development and decreased the levels of proinflammatory molecules in a murine model of atherosclerosis. Treatment with hematopoietic progenitors, EPCs or G-CSF may exert a major impact on vascular inflammation and atherosclerotic plaque development.
- © 2012 by American Heart Association, Inc.