Circulating Progenitor Cells Regenerate Endothelium of Vein Graft Atherosclerosis, Which Is Diminished in ApoE-Deficient Mice

Abstract

Previously we showed that a large number of endothelial cells in vein grafts undergo apoptosis or necrosis during the first few days followed by endothelial regeneration. In the present study, we investigated endothelial cell death and regeneration in vein grafts using transgenic mice carrying LacZ genes driven by an endothelial TIE2 promoter. When a vein fragment from TIE2-LacZ was isografted into the carotid artery of wild-type mice, the number of β-gal + cells were reduced at 3 days and disappeared completely by 4 weeks after grafting. Conversely, β-gal + cells were observed on the surface of vein segments donated by wild-type mice isografted into TIE2-LacZ mice at 1 week and reached confluence by 4 weeks, suggesting recipient origins of endothelial cells. Interestingly, β-gal + cells were evenly distributed on the surface of the whole vein segment grafted into TIE2-LacZ mice, indicating a contribution of circulating progenitor cells. When wild-type veins were grafted into a chimeric mouse carrying TIE2-LacZ genes in bone marrow cells, a proportion of cells displayed a β-gal + staining. Furthermore, the number of CD34 + and Flk + progenitor cells in blood of apoE-deficient mice were significantly lower than those of wild-type controls, which coincided with diminished β-gal + endothelial cells on the surface of vein grafts in TIE2-LacZ/apoE −/− mice. Thus, we provide the first evidence that endothelial cells of vein grafts are derived from circulating progenitor cells, of which one-third are derived from bone marrow progenitor cells. Hyperlipidemia due to apoE deficiency results in a lower number of endothelial progenitors in blood and correlated with enhanced atherosclerosis. The full text of this article is available online at http://www.circresaha.org.