Hypercholesterolemia contributes to the development of atherosclerosis and vascular remodeling by recruiting bone marrow-derived cells in cuff-induced vascular injury.
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 LDL-receptor 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 (alphaSMA)- and GFP-positive 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.
Xu
Yang
Y
Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Arai
Hidenori
H
Murayama
Toshinori
T
Kita
Toru
T
Yokode
Masayuki
M
D000199:Actins / Q000032:analysis; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology*; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D004036:Diet, Atherogenic; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005263:Femoral Artery / Q000293:injuries / Q000503:physiopathology*; D005487:Foam Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006937:Hypercholesterolemia / Q000150:complications*; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology
D000199:Actins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011973:Receptors, LDL; D049452:Green Fluorescent Proteins