Autologous vein grafts remain the only surgical alternative for many types of vascular reconstruction, although the patency rate is limited due to obliterative stenosis of the grafted vessels. The vascular remodelling occurs after vein graft due to altered biomechanical stress. We demonstrated that the earliest cellular event in mouse vein grafts is cell death, i.e. apoptosis and necrosis. Following endothelial death is cell regeneration, mononuclear cell infiltration and smooth muscle cell (SMC) accumulation, which form arteriosclerotic lesions. Endothelial cell repairs by stem/progenitor cells. Vascular endothelial cells in the areas where biomechanical stress alters may have a higher rate of death. It is a key issue to know how dead endothelial cells are replaced and which cells are responsible for regenerating the endothelium. To take advantage of transgenic animals, we developed and characterised a new animal model of vein graft atherosclerosis in wild-type and apoE-deficient mice. The lesion displayed classical complex morphological features and a heterogeneous cellular composition. By using transgenic mice expressing LacZ genes controlled by specific endothelial (TIE2-LacZ), SMCs (SM-LacZ) or all types of cells (ROSA26), we performed vein isografts in two types of transgenic mice expressing β-gal in endothelial cells and wild-type mice. We demonstrated that the endothelium on vein grafts completely disappeared due to apoptosis, and were replaced by progenitor cells, of which about one-third of cells were derived from bone marrow cells. These findings indicated the contribution of progenitor cells to regenerate damaged endothelium of the vessel wall. SMCs within atherosclerotic lesions are derived from progenitor cells. We observed that SMCs in mouse vein grafts appear in the neointima earlier than in the media after massive cell death, which is an early cellular event in the grafted vessels. Furthermore, a recent study demonstrated that smooth muscle progenitors were present in circulating blood, although their origins are unknown. Concomitantly, we showed that about 60% of SMCs in atherosclerotic lesions of vein grafts were derived from the donor vessel wall and 40% from recipients, possibly from circulating blood. These findings strongly suggest the possibility of progenitor cells being the source of smooth muscle accumulation in arteriosclerotic lesions. To explore the possibility of vascular progenitor cells for both smooth muscle and endothelial cells existing in adults, we provided the first evidence that the adventitia in aortas harboured large numbers of cells expressing stem cell markers, e.g. sca-1+ (21%), c-kit+ (9%), CD34+ (15%), Flk1 (4%) cells, but not SSEA-1+ embryonic stem cells, indicating that they are adult stem/progenitor cells. Finally, the mechanisms of stem/progenitor cell differentiation toward endothelial cells seem to depend on blood flow pattern. Support this notion is the finding that laminar shear stress induce stem cell differentiation into endothelial cells in vitro, in which growth factor receptor-HDAC-p21 signal pathways may be crucial. In summary, dead endothelial cells in vein grafts could be replaced by circulating stem cells. Functions and differentiating abilities of stem cells into endothelial cells might also be influenced by risk factors and local environment, i.e. biomechanical stress-influenced vessel remodeling mediated, to which stem cells contribute significantly.