Development and clinical application of novel anti-atherogenic drug.

新型抗动脉粥样硬化药物的开发及临床应用。

基本信息

批准号：
05557052
负责人：
KITA Toru
金额：
$ 10.88万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

We established assay system by which the inhibiting effect of monocyte adhesion to vascular endothelial cell is examined. The source of endothelial cells are from human umbilical vein. The endothelial cells were coincubating with or without Diisoprophyl-1,3-dithiol-2-ylidenemalonate or anti-VCAM-1 antibody and the inhibiting effect of these agents were examined. Unfortunately, the inhibiting effect of Diisoprophyl-1,3-dithiol-2-ylidenemalonate was limited, instead of repeat experiments. In case of anti-VCAM-1 antibody, experiments is undergoing. We use rabbit system, because we have an excellent animal model for familial hypercholesterolemia, WHHL-rabbit, which has severe cholesterolemia and atherosclerosis, since it is born. Therefore we chose VCAM-1 as an adhesion molecule for rabbit monocytes.It has been found that VCAM-1 molecules started to express on the surface of orifice for first intercostal artery at one month of age.In addition, the accumulation of monocytes were observed at the same area. At two month of age, the expression of VCAM-1 were found around the arterial wall at the place of first intercostal artery. At three month of age, T lymphocytes were seen at the same area. These phenomenon are first observation, so we are preparing the manuscript for publication. Recently VCAM-1 knockout mouse was made by other scientists. According to the study of knockout mouse, several adhesion molecules are involving the monocyte attachment onto endothelial cells in vivo. We are now searching adhesion molecules which are involving the monocyte attachment on the endothelial cells in vivo, besides VCAM-1 molecule.

我们建立了检测单核细胞对血管内皮细胞粘附的抑制作用的测定系统。内皮细胞的来源是人脐静脉。将内皮细胞与或不与1,3-二硫醇-2-亚基丙二酸二异丙酯或抗VCAM-1抗体共孵育，并检查这些试剂的抑制效果。不幸的是，Diisoprophyl-1,3-dithiol-2-ylidenemalonate 的抑制效果有限，无法重复实验。对于抗 VCAM-1 抗体，实验正在进行中。我们使用兔子系统，因为我们有一个优秀的家族性高胆固醇血症动物模型——WHHL-兔子，它从一出生就患有严重的胆固醇血症和动脉粥样硬化。因此我们选择VCAM-1作为兔单核细胞的粘附分子，发现VCAM-1分子在1个月龄时开始在第一肋间动脉口表面表达，并且观察到单核细胞的积累在同一区域。两个月龄时，在第一肋间动脉处的动脉壁周围发现VCAM-1的表达。三个月大时，在同一区域观察到 T 淋巴细胞。这些现象是第一次观察到，因此我们正在准备出版手稿。最近，其他科学家成功制作出VCAM-1基因敲除小鼠。根据基因敲除小鼠的研究，体内有几种粘附分子参与单核细胞对内皮细胞的附着。除了VCAM-1分子外，我们现在正在寻找涉及体内单核细胞附着在内皮细胞上的粘附分子。