The Effect And Mechanism Of Low Density Lipoprotein Concentration Polarization On Atherogenesis

Atherosclerosis is a chronic and synthetic disease. Atherosclerotic lesions are prone to develop at bifurcations, bends and junction of bypass points in vessels. Many theories and hypothesis were proposed to explain the mechanism of atherosclerosis, such as injure respond theory, monoclonal theory and inflammation theory. But all these theories can't sufficiently elucidate the localization of atherosclerosis. Deng et al hypothesized that the concentration polarization of atherogenic lipids, such as low density lipoprotein (LDL), might occur in the arterial system. That is, in the presence of filtration flow across the arterial wall, the lipids are accumulated at the blood/arterial wall interface, especially at regions of disturbed, recirculation or stagnation flow and low wall shear rates. The local highly concentrated LDL damages endothelial cells, then penetrates through endothelium and accumulates in subendothelium, further impacts the action of SMC and monocytes, which may promote the generation and development of atherosclerosis.Many chemokines, adhesion molecules and cytokines are involved in the development of atherosclerosis. Stromal cell–derived factor–1(SDF-1) is a chemokine with unique functions. SDF-1 and its receptor CXCR4 play important roles in regulating the migration, proliferation and chemotaxis of monocytes and stem cells. So we suppose that SDF-1/CXCR4 might regulate monocytes adhesion to endothelial cell, transendothelial migration and accumulation in subendothelium, which may play important roles in atherosclerosis formation and development induced by LDL concentration polarization.In order to further test the role of LDL concentration polarization on atherosclerosis localization, we simulated and tested the local hemodynamics at the down-stream of stenosis with numerical simulation and particle image velomecitry (PIV) separately,and then tested the concentration of LDL at wall in the down-stream of stenosis by use of numerical simulation and laser scan confocal technique. A cylinder with a round lumen was placed around the left carotid artery to format local stenosis, which was used to observe the effect of concentration polarization of LDL on atherosclerosis formation and development. After ringing, the rabbits were fed with the special formulated hyperlipotic or the standard chow for 4 or 8 weeks,then the two common carotid arteries of each rabbit were harvested to observe the role of LDL...