C.T. Lim and J.C.H. Goh (Eds.): WCB 2010, IFMBE Proceedings 31, pp. 402–405, 2010. www.springerlink.com Stromal Derived Factor-1 Is Up-Expressed in Atherosclerosis Lesion Induced by Low Density Lipoprotein Concentration Polarization D.H. Wei 1,2 , G.X. Wang 1, *, C.J. Tang 1 , J.H. Qiu 1 , J.B. Zhao 3 , H. Gregersen 3 , and L.H. Deng 1 1 Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College of Chongqing University, Chongqing, China 2 Key Laboratory for Arteriosclerology of Hunan Province (University of South China), The Institute of Cardiovascular Disease, Univer- sity of South China, Hengyang , China 3 Mech-Sense, Aalborg Hospital Science and Innovation Centre, Sdr. Skovvej 15, DK-9000 Aalborg, Danmark Abstract— In this study, we designed a animal model to de- tect the effect of LDL concentration polarization on athero- sclerosis 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 nor- mal or high fat/cholester food Numerical simulation and ex- perimental 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 im- munohistochemistry, RT-PCR and Western blotting, respec- tively. 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 expres- sion of SDF-1 were observed in the straight part of the seg- ment. 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. Keywords— Atherosclerosis, Concentration polarization, Low density lipoprotein, Low shear stress, Stromal derived factor-1. I. INTRODUCTION In the past years, many researches had emphasized the importance of wall shear stress in atherogenesis. It was suggested that local hemodynamic factors, in particular low endothelial shear stress (ESS), play a major role in localiza- tion of atherosclerosis. Low ESS modulates endothelial gene expression through complex mechanotransduction processes [1-4] and was an atherogenic factor to predict the localization and development of a high-risk plaque. Nevertheless, because of the fact that the early event leading to the genesis of atherosclerosis is the accumulation of cholesterol and other lipids within the arterial wall, in recent years more and more researchers believed that concentration polarization at the blood/arterial wall interface (a very well- known mass transfer phenomenon in engineering) might also play an important role in the localization and develop- ment of atherosclerosis in the human circulation [5]. Naiki and Karino verified that there was the concentration polari- zation phenomenon on the surface of a culture endothelial monolayer with 19 nm fluorescent microspheres [6]. Among various risk factors which are considered to cause and promote the vascular disease, the concentration of cho- lesterol carried by low-density lipoproteins (LDL) in blood has been considered the most important factor. Because the arterial wall is directly exposed to the concentration of atherogenic lipoproteins at the luminal surface, the concen- tration of LDL at this surface would do an important role in atherogenesis. Deng et al detected the LDL concentration distribution in a straight artery segment and proved that the luminal surface LDL concentration was 5%-14% greater than the bulk concentration under normal physiological flow conditions [7]. SHIGEO et al Using an isolated trans- parent human coronary artery to trace out the geometry of the multiple bend, found that the region where wall thicken- ing occurred also corresponds to the very region where surface concentration of LDL was locally elevated [8]. The findings strongly supported the LDL concentration- polarization theory on the localization of vascular diseases. The previous numerical simulation showed that because of regional differences in the near-wall blood flow velocity, blood pressure, and vascular permeability, the atherogenic lipid concentration at the luminal surface may vary accord- ing to locations in the arterial tree. We therefore hypothe- size that these local variations in the luminal surface lipid concentration may contribute to the localization of athero- sclerosis [9]. But to the best of our knowleage, the study of LDL concentration near artery wall was mostly performed using numerical simulation and only Wang et al measured the LDL concentration with a straight vessel [10]. More