Study for the initial event of athcrosclerosis.

在动物研究中显示的动脉粥样硬化的初始特征之一是循环单核细胞迁移到内皮下空间并发育成巨噬细胞。巨噬细胞将脂蛋白结合到细胞体中，并转化为载脂泡沫细胞，这是动脉粥样硬化早期的特征。然而，巨噬细胞仅具有少量的经典低密度脂蛋白（LDL）受体，并且以非常低的速率增厚天然LDL，这不足以在体外引起泡沫细胞形成。因此，脂蛋白在巨噬细胞中的掺入和代谢的其他机制吸引了研究者。据报道，这些细胞<beta>通过特异性受体-VLDL受体有效地整合来自Watanabe遗传性高胆固醇血症兔（家族性高胆固醇血症的动物模型）的-VLDL和VLDL<beta>。此外，巨噬细胞也被证明可以整合某些类型的化学物质， ...更多信息 烯丙基修饰的LDL。该途径首先针对乙酰-LDL显示，并且受体被称为乙酰-LDL受体。尽管这种受体的发现似乎解释了巨噬细胞在异位发生中的矛盾，但在体内尚未发现天然存在的LDL修饰形式。最近报道氧化LDL至少部分通过乙酰LDL受体被巨噬细胞有效摄取。由于脂质过氧化作用已被病理学或流行病学研究表明参与动脉粥样硬化形成，氧化LDL被认为是天然存在的修饰LDL的候选者。虽然巨噬细胞的泡沫细胞形成已被表明是动脉粥样硬化形成的关键事件之一，它是否仅仅是载脂细胞的积累过程或者对动脉粥样化的进展具有某些病理生理学作用还没有被阐明。1在这些物质中，花生四烯酸代谢产物越来越受到人们的关注，因为最近的研究表明它们与动脉粥样硬化的发生密切相关。然而，很少有人知道花生四烯酸代谢过程中的受体介导的脂蛋白的巨噬细胞和泡沫细胞的形成。因此，对这一点的研究将是有一定价值的，因为它可能给我们一个线索，以确定有孔虫细胞的功能作用，以确定它们是否作为动脉粥样硬化形成的促进剂。在这项研究中，我们培养小鼠腹腔巨噬细胞与脂蛋白和检测花生四烯酸代谢产物的生产与气相色谱-质谱和放射免疫分析。我们报告，氧化低密度脂蛋白刺激花生四烯酸代谢的巨噬细胞在其纳入细胞。少

One of the initial characteristics of atherosclerosis shown in animal studies is the migration of circulating monocytes into the subendothelial space and their development into macrophages. Macrophages incorporate lipoproteins into the cell body and get converted into lipid-laden foam cells, which are characteristically found in the early stage of atheroma. However, macrophages have only a few number of classical low density lipoprotein (LDL) receptor, and thke up native LDL at a very low rate, which is insufficient to cause foam cell formation in vitro. Therefors, investigators have been attracted to other mechanism of incorporation and metabolism of lipoproteins in macrophages. These cells have been reported to efficiently incorporate <beta>-VLDL and VLDL from Watanabe heritable hyperlipidemic rabbits, an animal model for familial hypercholesterolemia via a specific receptor, the <beta>-VLDL receptor. Moreover, macrophages were also demonstrated to incorporate certain types of chemic … More ally modified LDL. This pathway was first shown for acetyl-LDL and the receptor is called the acetyl-LDL receptor. Although the discovery of this receptor appeared to explain the paradox of macrophages in ahterogenesis, a naturally occurring modified form of LDL has not yet been identified in the body. Recently oxidized LDL has been reported to be efficiently taken up by macrophages at least in part by may of acetyl-LDL receptor. Because lipid peroxidation has been suggested to be involved in atherogenesis by pathological of epidemiological investigation, oxidized LDL is considered as a candidate for an example of naturally occurring, modified LDL.While foam cell formation of macrophages has been indicated to be one of the key events of atheroma formation, it has not been clarified yet whether it is only a process of accumulation of the lipid-laden cells or has some pathophysiological effects on the progression of atheroma. Macrophages release various biologically active substances when they are activated by phagocytic particles such as zymosan A or inflammatory stimuli such as lipopolysaccharideslAmong those substances, the products derived from arachidonate metabolism have attracted increasing attention, since recent studies have indicated their close relation to atherogensis. However, little is known yet about arachidonate metabolism during the process of receptor-mediated incorporation of lipoproteins by macrophages and foam cell formation. Studies on this lind, therefore, would be of some value, in as much as it might give us a clue for determining the functional role of the foram cells as to whether they act as a promotor for atheromatous formation.In this study, we incubated mouse peritoneal macrophages with lipoproteins and examined production of arachidonate metabolites with gas chromatography-mass spectrometry and redioimmunoassay. We report that oxidized LDL stimulates arachidonate metabolism in macrophages during its incorporation into the cells. Less