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Triglycerides rich lipoproteins and atherosclerosis: in vitro and in vivo studies

机译:甘油三酯富含脂蛋白和动脉粥样硬化:体外和体内研究

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The molecular mechanisms underlying the relationship between elevated plasma concentration of triglyceride-rich lipoproteins and coronary artery disease remain uncertain; evidence is accumulating to suggest that endothelial dysfunction is involved.In the present work, we addressed two major questions: First, we investigated the gene expression pattern and intracellular pathways in human endothelial cells incubated with very low density lipoproteins (VLDL) and oxidative modified VLDL (Ox-VLDL) Second, we investigated whether changes in RLP plasma levels during the postprandial phase relate to alterations of the endothelial function Results and conclusion Among 8411 genes spotted on the array, 1620 (192%) were expressed under basal condition VLDL predominantly activated the ERK1/2 pathway while P38 MAPK was the main target of Ox-VLDL, and CREB and NF-KB were activated by both VLDL.and Ox-VLDL VLDL induced MMP-2 and TGF alpha expression. Ox-VLDL was found to induce IL-15 and MIF expression, promote the generation of reactive oxygen species and exert a cytotoxic effect, thus sustaining inflammation and endothelial damage.These findings confirm the involvement of VLDL and Ox-VLDL in endothelial dysfunction and suggest new genes and molecular mechanisms involved in these actions.Moreover, cholesterol in RLPs contributes significantly to the endothelial dysfunction occurring during the postprandial lipemia.
机译:的分子机制富含甘油三酯的脂蛋白的升高的血浆浓度和冠状动脉疾病仍然不确定之间的关系基础;证据正在积累表明内皮功能障碍是involved.In目前的工作中,我们讨论了两个主要问题:第一,我们研究了与极低密度脂蛋白(VLDL)温育的人内皮细胞的基因表达模式和胞内途径和氧化改性VLDL (OX-VLDL)其次,我们研究了在餐后阶段变化在RLP血浆水平是否涉及到内皮功能结果和结论在8411个基因的改变的阵列,1620(192%)上点样物在基础条件下VLDL主要激活表达的ERK1 / 2途径而P38 MAPK是牛-VLDL和CREB和NF-KB的主要目标是由两个VLDL.and的Ox-VLDL VLDL活化诱导的MMP-2和TGFα表达。 OX-VLDL,发现诱导IL-15和MIF表达,促进活性氧的产生和发挥细胞毒性作用,从而维持炎症和内皮damage.These发现证实VLDL和OX-VLDL的在血管内皮功能障碍的参与和建议新基因和参与这些actions.Moreover分子机制,胆固醇在RLPS显著有助于餐后脂血症期间发生的内皮功能障碍。

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