| Atherosclerosis, the leading cause of death in the developed world and nearly the leading cause in the developing world, is a complicated disorder. Although any artery may be affected, the elastic arteries and large and medium-sized muscular arteries are the prime targets. There are many hypothesis on the development of atherosclerosis. But the response to injury hypothesis has been widely accepted. It states that the lesions of atherosclerosis are initiated as a response to some form of injury to arterial endothelium. The injury postulated is a form of endothelial dysfunction without necessary denudation, which increases permeability to plasma constituents, including lipids, and permits blood monocytes and eventually platelets to adhere to endothelium. Monocytes adhere and subsequently enter the intima, transform into macrophages, and accumulate lipid to become foam cells, contributing to the evolution of the lesion. Factors released from activated platelets at the surface or monocytes then cause migration of SMCs from media into the intima, followed by proliferation and synthesis of extracellular matrix components by SMCs, leading to the accumulation of collagen and proteoglycans. The luminal surface of the blood vessel and its endothelial surface are constantly exposed to hemodynamic shear stress. So, any change in blood flow could cause the change of endothelium. Atherosclerotic lesions long have been known to occur near vascular branching points. Studies have identified in these predisposed areas, hemodynamic shear stress, the frictional force acting on the endothelial cell surface as a result of blood flow, is weaker than in protected regions. So from the view of cellular rheology, we examined the influence of fluid shear stress on the metabolism, morphology, structure and function of endothelia cells. One of the early events of atherosclerosis is the recuit of monocytes into the subendothelium. Monocyte chemoattractant protein-I (MCP-I), a chemokine that is expressed in the development of atherosclerosis lesions, is thought to play a major role in stimulating the migration of blood monocytes into the artery wall. MCP-1 can be produced by many kinds of cells. But in the early stage of atherosclerosis, it is mainly secreted by ECs. In this experiment, ~ve assessed the effects of shear stress on MCP-I 昿rotein expression and secretion by endothelial cells with sensitive and convenient techniques. In this study, we culture human umbilic vein endothelial cells (HUVEC) and apply different levels of fluid shear stress to them by a parallel plate flow chamber, then see the change of MCP-l. The major methods employed are immunohistochemistry and ELISA. With immunohistochemistry method, we observe synthesized MCP-I in the cellular plasma and measure it by digital image analysis method. The result shows that synthesized MCP-I was 3 few after 0.5 h and was significantly increased after 2 h and 5 h, then was decreased after a period of 6h with shear stress of 4 dynlcm2 applied. When a shear stress of 10 dynlcm2 was applied, the change is not so obvious. Then with the method of ELISA, we measured MCP-1 in the perfusion after applying shear stress. The results of the experiment demonstrated the increase of MCP- 1 secretion by shear stress was time- and force-dependent. The accumulated level of MCP- I in I-lU VEC under shear stress of 4 dynlcm2 for Shr was 3-fold compared with that for Static cells. When the shear stress laste... |
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