| Project/Area Number |
09670698
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ETO Masato (1998) The University of Tokyo, Dept of Geriatrics, Assistant Professor, 医学部・附属病院, 助手 (80282630)
長野 宏一朗 (1997) 東京大学, 医学部附属病院, 助手 (30282627)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIZUMI Masao The University of Tokyo, Dept of Geriatrics, Lecturer, 医学部・附属病院, 助手 (20282626)
TOBA Kenji The University of Tokyo, Dept of Geriatrigs, Assistant Professor, 医学部・附属病院, 助教授 (60155546)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Oxidant Stress / Estradiol / Endothelial Cell / Apoptosis / BAX / エストロゲン / 内皮新生 / 新生内膜肥厚 / 血管内皮 / フリーラジカル / 過酸化水素 / 動脈硬化 / 遺伝子産物 |
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| Research Abstract |
It has been shown that reactive oxygen promotes athelosclerosis. On the other hand, 17beta-estradiol (E2) is shown to ha* inhibitory effect on lipid oxidation. Therefore, we investigated whether E2 inhibits H202-induced apoptosis of EC.
In vitro study
[Materials and Methods] Bovine carotid endothelial cells (BCEC) were cultured in phenol red free medium added wi* E2 (10^<-6>-10^<-12>M) for 24 hours prior to exposure with 0.1mM H202 (30 min.). Morphological changes were examin using a fluorescent DNA binding dye (Hoechst 33342). Furthermore, DNA fragmentation was confirmed on agaro gel electrophoresis. EC cell viability was quantified by (MTT) assay.
[Results] Cell shrinkage, cytoplasmic and nuclear condensation, cell blebbing, and apoptotic bodies were determined EC treated with H202. DNA ladder pattern was found regardless of the preteatment with E2. E2 had no effect * extracellular concentration of H202. In MTT assay, E2 increased cell viability. In addition, H202 induced-apoptosis was significantly inhibited by E2 in a dose-dependent manner. E2 treatment suppressed BAX expression but had no effe* on Bcl2 or P53 expression. These results suggests that E2 inhibits H202 induced BC apoptosis via the suppression BAX protein.
In vivo study
Estrogen replacement attenuates the increased risk for cardiovascular disease in postmenopausal women. Besides * influence on lipid profiles, estrogen acts directly on the vascular wall. Recent studies have shown using in vitro cultu* system that estrogen inhibits endothelial cell (EC) apoptosis which may play an important role in atherogenes. However, in vivo relevance of this finding is not elucidated. To do so, we have established a rat vascular injury model which intraarterial administration of hydrogen peroxide induces EC apoptosis. We demonstrate that estrogen replacement in ovariectomized rats protects EC apoptosis by <approximately equal> 50%, resulting reduced neointima form
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