Effects Of GM3 On Endothelial Cells Stimulated By LPS Or OX-LDL

Solid previous studies have uncovered that compared with healthy vessels the expression in cells and the release in extracellular matrix of ganglioside GM3 dramatically increase in atherosclerotic human or animal vessels. On the other hand, a growing body of evidence suggests that both exogenous and endogenous GM3 can significantly influence the behaviors(e.g., cell adhesion, proliferation, migration, etc.) of many cell types, including cancer cells, fibroblasts, epithelial cells, among others. Therefore, we hypothesize that the significantly increased ganglioside GM3 as a result of atherosclerosis may in turn influence the oxidation of low-density lipoproteins(LDL)and the behaviors of the cells in atherosclerotic plaques, based on which the initiation and progression of the atherosclerosis will finally be modified. Therefore, This project will detect the underlying molecular mechanisms of, the potential functions of GM3 in the initiation or progression of the atherosclerosis. We hope that the study will provide implications for further understanding or the cure of this disease.In order to explore the influence of the added exogenous GM3 on the adhesive property of mononuclear cells onto endothelial cells and on the expression quantity of adhesion molecule ICAM – 1,the research utilizy LPS and OX- LDL induced human umbilical vein endothelial cells as the model and use immunofluorescence staining and flow cytometry, agarose gel electrophoresis to conduct experiments.We confirmed the following conclusions from experimental results: 1000ng/ml bacterial lipopolysaccharide and 50ug/ml oxidized low density lipoprotein by respectively activating endothelial cells, cause the increase of the expression quantity of adhesion molecule ICAM-1, further leading to the significant increase of adhesive mononuclear cells. With the addition of exogenous 40ug/ml GM3, the expression quantity of adhesion molecule ICAM-1 of endothelial cells decreases and accordingly the number of adhesive mononuclear cells also drops apparently.Monocyte adhesion to endothelial cells is a key step to the formation and develop ment of atherosclerosis. Therefore, the above results show that a high content of GM3 microenvironment would probably Influence the process of atherosclerosis through intervening this critical step. The further studies would explore the influence of high content of GM3 microenvironment on the behavior of other cells(such as migration, foam and proliferation or apoptosis of macrophages and smooth muscle cells etc.)to elaborate the possible role and mechanisms of GM3 in the formation and development of atherosclerosis.