Recently, the role of bone marrow (BM)-derived endothelial cells and smooth muscle cells (SMCs) has been extensively studied in the pathogenesis of atherosclerosis. In this study we examined the effect of hypercholesterolemia on cuff-induced intimal thickening in LDLreceptor knockout (LDLR-/-) mice fed with a high-fat diet. We transplanted BM of green fluorescence protein (GFP)-transgenic mice to LDLR-/- mice to identify the cell lineage in the lesion. After BM transplantation mice were fed with a high-fat diet for 4 weeks and were then planted a polyethylene cuff on the right femoral artery. Two weeks after cuff placement, atherosclerotic lesions developed in the intima predominantly consisting of a massive accumulation of foam cells with a number of alpha smooth muscle actin (alpha SMA)- and GFPpositive cells. Adventitial small vessels were positive both for CD31 and GFP. Our data indicate that BM-derived cells can contribute to the development of atherosclerosis in the presence of hypercholesterolemia. (C) 2007 Elsevier Inc. All rights reserved.