Infusion of lin-/sca-1+ and endothelial progenitor cells improves proinflammatory and oxidative stress markers in atherosclerotic mice

Abstract

Background: The effects of direct infusion or indirect mobilization of progenitor cells on atherosclerotic plaque development and progression are not clear. We sought to investigate the effects of hematopoietic progenitors lineage negative/stem cell antigen-1 positive (lin-/sca-1+) cells, endothelial progenitor cells and G-CSF administration on the inflammatory and oxidative component of atherosclerosis.

Methods: Splenectomized ApoE(-/-) C57BL/6J mice (6-8 weeks of age) fed with a high-fat, cholesterol-rich diet for 6 weeks, 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. sVCAM-1 (Vascular cell adhesion protein 1), sICAM-1 (soluble intercellular adhesion molecule-1), sE-Selectin, Metalloproteinase 9 (MMP-9), Plasminogen activator inhibitor (PAI-1), Interleukin 6 (IL-6), oxidized LDL (ox-LDL) levels and lipid PEROX were evaluated at the day of the first infusion, 7 days later and 6 weeks post-treatment with ELISA.

Results: The administration of both G-CSF and progenitor cells significantly decreased the levels of sICAM-1, sVCAM-1,sE-Selectin, IL-6, ox-LDL and lipid Perox 6 weeks after the initiation of treatment. No significant effects of lin-/sca-1+ cells, EPCs and G-CSF on PAI-1 and MMP-9 levels were observed. The effects of all treatments on the levels of pro-inflammatory molecules and oxidative stress parameters 7 days post-treatment were not significant. Interestingly, the levels of sICAM-1and sE-selectin were increased 7 days post-treatment.

Conclusions: Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells significantly decreased the levels of proinflammatory molecules and oxidative stress parameters in a murine model of atherosclerosis. The principal novelty of this work is that treatment with hematopoietic progenitors, EPCs or G-CSF may exert beneficial effects on vascular inflammation and atherosclerotic plaque development.

Keywords: Endothelium; Inflammation; Oxidative stress; Progenitor cells.