| Project/Area Number |
06557054
|
|---|
| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | University of Tokyo |
|---|
Principal Investigator |
KODAMA Tatsuhiko The Third Department of Internal Medicine, University of Tokyo, 医学部(病), 助手 (90170266)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KITA Toru Dept.Gerontology, Univ.Kyoto, 医学部, 教授 (60161460)
DOI Takefumi Pharmacetical Science, Univ.Osaka, 薬学部, 助教授 (00211409)
WADA Yoichiro 3rd Dept.Int.Med, Univ.Tokyo, 医学部(病), 医員
NAKAJIMA Atsushi 3rd Dept.Int.Med, Univ.Tokyo, 医学部(病), 医員
MATSUHASHI Nobuyuki 3rd Dept.Int.Med, Univ.Tokyo, 医学部(病), 助手 (10221590)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Project Status |
Completed (Fiscal Year 1995)
|
| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 1995: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1994: ¥8,500,000 (Direct Cost: ¥8,500,000)
|
|---|
| Keywords | microphage / scavenger recepto / atherosclerosis / lipoprotein / host defense / mouse genetics / endocytosis / adhesion molecule / 酵素ラジカル / コレステロール / 動脈硬化 / 発生工学 / ジーンターゲッティング / リポ蛋白 |
|---|
| Research Abstract |
In order to develop a novel therapeutic approach, over 600 novel type of lipophilic antioxidants were synthesized and analyzed. Some of them are very potent to prevent oxidation of LDL in vitro and were absorbed well by experimental animals without any serious side effects. Two of them, LDL-antioxidant 1 (LAO-1) and LAO-2 were analyzed in WHHL rabbits, mice model of atherosclerosis and post PTCA stenosis model in rabbits. These drugs (LAO-1and2) are useful for the prevention of atherosclerosis in WHHL rabbits and also for the prevention of atherosclerosis in C57BL6-high cholestarol diet model. These compounds inhibit the the development of post-baloon injury stenosis. The growth of vascular smooth muscle cell after the cytokine stimulation was inhibited by these compounds. Probucol, an potent LDL antioxidant was effective for the prevention of WHHL rabbit atherosclerosis, but probucol exaggerated the atherosclerosis in LDL receptor deficient mice and apo E deficient mice, which was not seen after LAO-1 or 2 administration.
|
