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Variant Endothelial cells of human aorta

人主动脉变异内皮细胞

基本信息

批准号：
02807041
负责人：
TOKUNAGA Osamu
金额：
$ 0.96万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

1) Endothelial cells in primary culture were morphologically classified into two types : typical endothelium and variant endothelium. Typical endothelial cells were small, round to polygonal, and arranged uniformly. Variant endothelial cells were larger, ranging from 100 to 200 um, and sometimes more than 250 um in diameter with multinuclei. The ratio of variant endothelial cells to typical cells correlated well with the severity of atherosclerosis than with aging and it was confirmed in experimental atherosclerotic rabbits. Variant endothelial cells can be formed by denatured LDL, interleukin-4 and oxyradicals in vitro.2) To investigate the functional alteration of human aortic endothelial cells with aging, prostacyclin synthesis was qualitatively and quantitatively examined, and also immunohistochemically examined. endothelial cells, the young group synthesized the largest amount of prostacyclin in a conventional culture condition, with synthesis progressively decreasing in the older groups. Immunohistologically, endothelial cells in young aortas revealed intensely positive for prostacyclin, but the intensity of aortic endothelial cells from older subjects was low. Smooth muscle cells in the thickened intima of the aorta were weakly immunoreactive. The decreased synthesis of prostacyclin with age may play an important role in the development and advancement of thrombosis and atherosclerosis.3) Interaction between endothelial cells and inflammatory cells or monocytes/macrophages is currently underinvestigation.4) Although not directly related to this project, we developed a method of enzyme-linked immunohistochemistry for detection of "endothelin" useful on formalin-fixed and paraffin embedded sections.

1)原代培养的内皮细胞在形态学上可分为典型内皮细胞和变异内皮细胞。典型的内皮细胞较小，圆形至多角形，排列均匀。变异的内皮细胞较大，直径在100 - 200 μ m之间，有时直径超过250 μ m，具有多核。变异内皮细胞与典型内皮细胞的比例与动脉粥样硬化的严重程度相关，而与年龄相关，并在实验性动脉粥样硬化家兔中得到证实。体外实验表明，变性LDL、白细胞介素4和氧自由基可诱导内皮细胞发生变异。2）为探讨人主动脉内皮细胞功能随衰老的变化，对人主动脉内皮细胞前列环素合成进行了定性、定量和组织化学检测。在内皮细胞中，年轻组在常规培养条件下合成最大量的前列环素，而在老年组中合成逐渐减少。免疫组织学检查显示，年轻人主动脉内皮细胞前列环素呈强阳性，但老年人主动脉内皮细胞的强度较低。主动脉内膜增厚的平滑肌细胞呈弱免疫反应性。随着年龄的增长，前列环素的合成减少，这可能在血栓形成和动脉粥样硬化的发展中起重要作用。3）内皮细胞与炎症细胞或单核细胞/巨噬细胞之间的相互作用目前尚不清楚。4）尽管与本项目没有直接关系，但我们开发了一种酶联免疫组化方法，用于检测福尔马林固定和石蜡包埋切片上的“内皮素”。