Abstract 966: Endogenous Mobilization of Endothelial Progenitor Cells Improves Endothelial Function and Reduces Neointima Formation in Mice
Endothelial cell damage plays an important role in atherogenesis and restenosis after angioplasty. Endothelial restoration may be affected by circulating progenitor cells. We investigated the effect of endogenous mobilization of endothelial progenitor cells (EPCs) on endothelial dysfunction and neointima formation in mice.
Methods and Results: Wild-type (C57BL6) mice were treated with either erythropoietin (EPO; 1 U/g body weight/d), G-CSF (0.05 μg/g/d) or the HMG-CoA reductase inhibitor rosuvastatin (Rosu; 10 mg/kg/d) subcutaneously for 10 days. FACS analyses of peripheral blood revealed a significant increase of circulating sca-1/flk1-positive EPCs after treatment with EPO, G-CSF, or Rosu. The effect of endogenous EPC mobilization on neointima formation was investigated after endothelial wire injury of the carotid artery. Wild-type mice were subjected to carotid injury and treated with EPO, G-CSF, or Rosu for 10 days after injury. Active treatment caused enhanced reendothelialization of the carotid artery lesion and led to a significant reduction of neointima formation as compared with placebo-treated animals. To assess the relevance of EPC mobilization for endothelial function, apolipoprotein E-deficient (ApoE−/−) mice were treated with high-cholesterol diet containing 1.25% cholesterol for 6 weeks. These mice were co-treated with EPO, G-CSF, or Rosu for the last 10 days of high-cholesterol diet. Placebo-treated ApoE−/− mice showed marked impairment of endothelium-dependent vasodilation as compared with wild-type mice (organ chamber experiments with isolated aortic segments). Importantly, treatment with EPO, G-CSF, or Rosu led to significant improvement of endothelium-dependent vasodilation.
Conclusions: Endogenous mobilization of endothelial progenitor cells by various pharmacological stimuli is associated with an improvement of endothelial dysfunction and a reduction of neointima formation after carotid injury. These results underline the importance of endothelial progenitor cells for vascular function and integrity and demonstrate the possible therapeutic potential of pharmacological mobilization of progenitor cells for the treatment of vascular disease.