| Atherosclerosis is not merely a disease in its own right, but a process that is the principal contributor to the pathogenesis of myocardial and cerebral infarction, gangrene, and loss of function in the extremities. Despite the universal occurrence of atherosclerosis in the world, the pathogenesis of disease remains incompletely understood. In the injury theory of R.Ross, atherosclerosis can be considered to be a modified form of chronic inflammation induced by lipids, and many have followed in this path.Macrophage-derived foam cells are characteristic pathological cells in the lesions of atherosclerosis. During the process of atherosclerosis, monocytes and oxidized-low density lipoprotein (ox-LDL) seem to play a central role. Once monocytes adhere to the subendothelial space and enter into the intima of the artery, ox-LDL and other substances associated with atherogenesis may participate in transformation of the monocytes into macrophage. Uptake of ox-LDL by the macrophages through scavenger receptors will lead to foam cells formation. The macrophage-derived foam cells not only result in formation of fatty streaks, which are believed to represent the earliest type of atherosclerotic plaque, but also play a role in the fibroproliferative process by their capacity to form numerous growth factors and numerous cell adhesion molecules. This study aimed to determine the expression kinetics of ICAM-1 and VEGF in dose response and time course in U937 foam cells, and further investigate the global changes in protein expressions between the U937 foam cells and the control U937 cells using proteomic technologies. To understand the effects of Sal B and GbE on the inflammatory reactions in AS, the regulation effects of drugs on ICAM-1 and VEGF expressions in foam cells were determined.Rat was considered suitable for many cardiovascular model establishment including cardiac hypertrophy, hypertension, heart failure, but not easy in atherosclerosis for its hyperlipidemia-resistant character. Recently, we combined the high fat /cholesterol diets containing sodium cholate and propyl-thyracil with injection of vitamin D3, which led a new way to establishment of an experiment atherosclerotic model in rats. The different expression kinetics of growth factor and adhesion molecule led a major initiative in our laboratory to determine the expression patterns in this atherosclerotic rat model to gain further evidences in vivo. This study aimed to determine the expression patterns and mRNA levels of ICAM-1 and VEGF in atherosclerotic rats during the time course. We are also using novel proteomics approachs to identify new proteins in process of coronary AS tissues and the serum.Recently, more and more studies have stressed on the abilities of proteomics in providing new way for the investigations of novel drug target proteins. In this stud, protecitve roles of drugs in pathological models of AS, such as atherosclerotic rat, foam cells induced by oxidized low-density lipoprotein, are investigated by proteomic meathods including two-dimensional gel and biological mass spectrometry. Through the comparative study of proteome, as well as identification and functional analysis of the correlated proteins, drug target and effector proteins are analyzed, aiming to seek several novel proteins in the protective roles in AS.The progress of this study were presented in four part:1. The expressions of VEGF and ICAM-1 in foam cells and the regulation of drugs(1) The foam formation was formed after U937 cells treated with ox-LDL. After U937 cells incubated with ox-LDL and treated withOil red O, many red pellets were found in the plasma of the U937 cells. (2) VEGF and ICAM-1 expressions in foam cells were confirmed by immuno- histochemistry, flow cytometry, ELISA, and Northern blot; VEGF asODN could inhibit the VEGF expressions.(3) Kinetic studies showed the deferent kinds of expression curves in dose response and time course, which proved that both ICAM-1 and VEGF expressions were enhanced in the macrophage-derived foam cells, but I... |
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