['Recently, it has been shown that stem/progenitor cells may repair damaged/lost endothelial cells in vein grafts and wire-injured arteries. In the present study, we investigated endothelial cell turnover and regeneration in apolipoprotein E (apoE)(-/-)/transgenic mice carrying LacZ genes driven by an endothelial TIE2 promoter.', 'To assess cell proliferation on the surface of aortas in apoE(-/-) mice and wild-type controls, BrdU was injected into the tail vein and labeled on en face preparation. BrdU-positive cells on the aortas were observed occasionally in wild-type mice and frequently at sites prone to lesion development in apoE(-/-) mice (0.18+/-0.1% versus 1.12+/-0.2%; P<0.001). Endothelial integrity tests demonstrated that the areas with high rate of cell turnover displayed Evans blue leakage, low levels of VE-cadherin expression, and increased cell attachment, as evidenced by Evans blue dye injection, immunostaining, and scanning electron microscopy, respectively. Furthermore, immunostaining for CD34, Sca-1, Flk-1, and CD133 indicated that approximately 3% to 5% of total cells on the aorta were positive in apoE(-/-) mice. En face double labeling using Ki-67 and progenitor markers revealed that 30% to 50% of progenitor(+) cells expressed Ki-67, indicating a state of proliferation. To clarify the origin of endothelial progenitor cells participating in endothelial repair in apoE(-/-) mice, a chimeric mouse model was created by bone marrow transplantation between apoE(-/-) and LacZ(+/+)/apoE(-/-) mice. Ten months after bone marrow transplantation, approximately 3% to 4% of total cells in the lesion-prone areas were beta-gal positive in apoE(-/-) with apoE(-/-)/TIE2-LacZ bone marrow mice. When cells of aortas from chimeric mice were cultivated on Matrigel-coated plates, a capillary-like structure was found, which showed beta-gal/CD31 or beta-gal/von Willebrand factor double positivity. By a combined analysis of laser dissection microscopy and nest reverse transcription polymerase chain reaction, it was found that beta-gal(+) cells were mainly expressing CD31 and CD144.'] Does rapid endothelial turnover in atherosclerosis-prone areas coincide with stem cell repair in apolipoprotein E-deficient mice?