| Project/Area Number |
61480208
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
FUKUZAKI Hisashi Kobe University School of Medicine,Professor, 医学部, 教授 (90030824)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAHARA Yasuhiro Kobe University School of Medicine,Assistant professor, 医学部, 助手 (80169755)
WATANABE Yoshio Kobe University School of Medicine,Institute for Animal Reserach Assoclate Profe, 医学部附属動物実験施設, 助教授 (00031401)
ISHIKAWA Yuichi Kobe University School of Medicine,Lecturer, 医学部, 講師 (90159707)
YOKOYAMA Mitsuhiro Kobe University School of Medicine,Associate Professor, 医学部, 助教授 (40135794)
高野 新二 神戸大学, 医学部附属病院, 講師 (30116222)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | Atherosclerosis / PDGF / cholesterol metabolism apolipoprotein / sugar chain / アポ蛋白 / アスパラギン結合糖鎖 / 動脈硬化症 / 細胞増殖因子 / Cキナーゼ / カルシウム |
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| Research Abstract |
To elucidate the mechanisms of the initiation and development of atherosclerosis,the following investigations were carried out.
1. The interaction of platelets and vascular walls. The helical strips of coronary artery isolated from normal and WHHL rabbit were incubated in an organ with oxygenated Krebs-Henseleit solution. The isometric tension was recorded. The contractile responses to platelets were well correlated to the numbers of platelets stimulated with thrombin. This contraction was inhibited by methysergide (5HT antagonist) but not by Ketanserin (5HT_2-selective antagonist).
The dose-response curve showed that exogenous 5HT contracted the helical strips at lower concentration (10^<-10>M) than histamine (10^<-7>M). The maximum contraction was obtained by histamine. The contractile responses to ergonovin in WHHL rabbits were greater than normal. The progression of atherosclerosis intensified the contractile responses to the ergonovine.
2. Cell Growth and PDGF In Swiss 3T3 cells,PDGF
… More
binding to cell membrane stimulated phospholipase C PIP_2 was degraded to DG and IP_3. DG activated protein kinase C and IP_3 mobilized Ca^<++> ion from sarcoplasmic reticulum.At the same time, The amount of mRNA of c-myc gene was increased. Both TPA and OAG increased mRNA of c-myc gene without the mobilization of Ca_<++>. A23187 increased mRNA of c-myc gene without activation of protein kinase C. The synthesis of DNA was increased in PDGF stimulated cells only shen insulin was added.Those findings were also observed in rabbit cultured vascular smooth muscle cells.
3. The mechanisms of lipid accumulation In isolated mouse peritoneal macrophages, the association of ^<125>I-<beta>VLDL was incresed by the calcium blockers,nifedipine and TMB-8. The degradation of ^<125>I-<beta>VLDL was also increased in the presence of calcium blockers. It was suggested that Ca^<++> might have the impotant role in cholesterol metabolism. 4. The structures of asparagine-linked sugar chains of apolipoprotein B-100. The analysis of sugar chains of Apo-B showed that Apo B contained neutral(N)and two different acid sugar chains (A_1,A_2) The ratio was 3:4:3 respectively. The roles of sugar chains remained to be investigated. The furter investigations will be performed to elucidate the mechanisms of atherosclerosis. Less
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