Stromal Derived Factor-1 Is Up-Expressed in Atherosclerosis Lesion Induced by Low Density Lipoprotein Concentration Polarization

Abstract

In this study, we designed a animal model to detect the effect of LDL concentration polarization on atherosclerosis and explore the molecular mechanism. A method to induce a defined local stenosis in straight segment of rabbit left carotid artery was developed. The rabbits were fed with normal or high fat/cholester food Numerical simulation and experimental measurement were used to analyze the feature of the blood flow and the LDL distribution. The arterial lesions were evaluated by using HE staining, collagen staining, Oil red O staining and High performance Liquid Chromatography. The expression of stromal derived factor-1 (SDF-1) in the lesions and cultured endothelial cells were analyzed with immunohistochemistry, RT-PCR and Western blotting, respectively. Results showed that the blood flow was disturbed and the shear stress decreased at the distal of stenosis significantly. The LDL concentration polarization took place at the distal of stenosis and the concentration of LDL was 35% higher in the arterial wall than in the lumen. The atherosclerotic lesion was formed and SDF-1 was expressed in the arterial segment distal to the stenosis, whereas no atherosclerotic lesion and expression of SDF-1 were observed in the straight part of the segment. It was in vitro cell culture experiment showed that LDL induced monocyte adherence to the endothelial cells and such effect could be inhibited by SDF-1 antibody.