1994 Fiscal Year Final Research Report Summary
Development and clinical application of novel anti-atherogenic drug.
| Project/Area Number |
05557052
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KITA Toru Kyoto University, Faculty of Medicine, Professor, 医学部, 教授 (60161460)
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| Co-Investigator(Kenkyū-buntansha) |
HAMAGUTHI Hiroshi Nihon Nohyaku Co., Ltd., Director, 医薬研究所, 主任研究員
WAKATSUKI Yoshio Kyoto University, Faculty of Medicine, Instructor, 医学部, 助手 (40220826)
KUME Noriaki Kyoto University, Faculty of Medicine, Instructor, 医学部, 助手 (20252455)
YOKODE Masayuki Kyoto University, Faculty of Medicine, Lecturer, 医学部, 講師 (20252447)
DOI Toshio Kyoto University, Faculty of Medicine, Lecturer, 医学部, 講師 (60183498)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Atherosclerosis / Monocyte / Vascular endothelial cell / Macrophage / Monocyte adhesion molecule / WHHL-rabbit / VCAM-1 / Tlymphocyte |
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| Research Abstract |
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.
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