| Project/Area Number |
04454274
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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 | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
NAKASHIMA Yasuhide UOEH,School of Medicine, Associate professor, 医学部, 助教授 (20038780)
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| Co-Investigator(Kenkyū-buntansha) |
SUGANO Masahiro UOEH,School of Medicine, Asistant professor, 医学部, 助手 (20206395)
TAKAHARA Kazuo UOEH,School of Medicine, Lecturer, 医学部, 講師 (30163306)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1992: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | Low-density lipoprotein / arterial smooth muscle cell / Intracellular Ca^<2+> / free cholesterol / フリーコレステロール / 動脈硬化退縮 / プロブコール / ヂルチアゼム / イノシトール三リン酸 / LDL / SMC / Ca^<++> |
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| Research Abstract |
To elucidate the mechanism of low-density lipoprotein (LDL) from familial hypercholesterolemic (FH) human subjects on the cultured smooth muscle cell (SMC), cell proliferation, Ca2+ movements and membrane structure were examined, along with the antiproliferative action of heparin or sulfated glycosaminoglycans. Cell growth as well as Ca^<2+> uptake was stimulated in a concentration-dependent fashion with FH-LDL compared to control (without LDL). With methylated LDL, which had no capacity to bind LDL receptor, the proliferation and Ca2+ uptake were still significantly increased compared to control. But the about 60% of increase over control was reduced by methylation. In analysis of lipid composition, the exposure to FH-LDL elevated free cholesterol contents in SMC membrane. In structural analysis, FH-LDL brought the swelling in the intrabilayr and interbilayr structure compared to control, which well correlated with change in the increase in free cholesterol in plasma membrane. Heparin or sulfated glycosaminoglycans inhibited the cell proliferation with reduction of free cholesterol in plasma membrane. We concluded that FH-LDL might increase the free cholesterol composition in plasma membrane through LDL receptor-independent pathway, and that change structure of membrane, which affect Ca2+ channel function.
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