2004 Fiscal Year Final Research Report Summary
Mechanisms of morphological and functional changes of endothelial cells in atherogesesis.
| Project/Area Number |
14570204
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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 |
Experimental pathology
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| Research Institution | Nihon University |
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Principal Investigator |
MITSUMATA Masako Nihon University, Dep.Pathology, School of Medicine, Professor, 医学部, 教授 (40064589)
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| Co-Investigator(Kenkyū-buntansha) |
KUSUMI Yoshiaki Nihon University, Dep.Pathology, School of Medicine, 医学部, 講師 (60186393)
NIIHASHI Mari Nihon University, Dep.Pathology, School of Medicine, 医学部, 講師 (70155860)
IWASA Satoshi Nihon University, Dep.Pathology, School of Medicine, 医学部, 講師 (40328745)
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| Project Period (FY) |
2002 – 2004
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| Keywords | atherosclerosis / endothelial cells / shear stress / apoptosis / cell proliferation / monocyte adhesion / MMP-2 / en face method |
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| Research Abstract |
1.To disclose the anti-atherosclerotic mechanisms of steady laminar shear stress, we analyzed the expression of human inhibitor of apoptosis protein-2(HIAP-2) in endothelial cells(ECs). HIAP-2 was dose-dependently and time-dependently induced in ECs by shear stress. HIAP-2 expression also identified in vivo. Shear stress-mediated inhibition of EC apoptosis was associated with inhibition of caspase-3 activity. Transfection of Smac, a caspase activator by binding HIAPs and removing their inhibitory activity, reduced the suppression effect of shear stress on caspase-3 activity. These data suggest that shear stress prevents EC apoptosis via negative regulation of caspase-3 by increments of HIAP-2. 2.The MMP2 secretion from ECs into medium was interrupted completely by laminar shear stress, although level of this intracellular protein and mRNA expression of MMP2 were unchanged. To clarify this mechanism, we analyzed intracellular transportation of MMP-2, using fused MMP-2 tagged with GFP. B
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y laminar shear stress, MMP-2/GFP granules increased their size and transported into cell membrane without secretion. Our data suggest that laminar shear stress contribute to EC adhesion on matrix through the regulation of collagen type IV metabolism. 3.To analyze a initial events of atherosclerosis, in vivo, we established a modified en face method that enabled us to obtain clear images of the entire surface of endothelium including a bifurcation orifices of aorta, where atherosclerosis initiates. A number of proliferating ECs and macrophages adhered on ECs, stained with specific antibodies, at the branching area of aorta from SD rats were about 2 and 3 times higher than that of non-branching area, respectively. In conclusion, stabilization of ECs through the regulation of cell death, cell growth, EC adhesion on matrix with control of collagen metabolism and inhibition of monocyte adhesion on ECs by the laminar shear stress may contribute to the formation of the anti-atherosclerotic microenvironment in vessels. Less
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Research Products
(6 results)
