2005 Fiscal Year Final Research Report Summary
Stability of the basement membrane of vascular endothelium by shear stress
| Project/Area Number |
16500288
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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 |
Biomedical engineering/Biological material science
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| Research Institution | University of Yamanashi |
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Principal Investigator |
YAMANE Tetsu University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Research Associate, 大学院・医学工学総合研究部, 助手 (60220430)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIYA Akira Nihon University, Graduate School of Business, Professor, 大学院・グローバル・ビジネス研究科, 教授 (50014072)
MITSUMATA Masako Nihon University, School of Medicine, Professor, 医学部, 教授 (40064589)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Atherosclerosis / Shear stress / Vascular endothelium / Basement membrane collagen / Matrix metalloprotease / Caveola |
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| Research Abstract |
Extracellular matrix (ECM) including subendothelial basement membrane (BM) developed more in the anti-atherosclerotic regions, which are exposed to laminar high shear stress, than in the atherosclerotic-prone regions, which are exposed to turbulent low mean shear stress. We present evidence that laminar shear stress by blood flow influences the subendothelial ECM architecture through the regulation of endothelial collagen metabolism.
Methods ; Endothelial cells (EC) obtained from bovine aorta and human umbilical veins were exposed to laminar shear stress using parallel-plate flow chamber.
After exposure, collagenase sensitive products labeled with 3H-proline were measured as collagenous protein, and analyzed by fluolography. Expression of Matrix metalloprotease-2 (MMP-2), which degrades type IV collagen as main component of BM, was analyzed with gelatin zymography, western blotting and northern blotting.
Results : 1) Type IV collagen synthesis of EC was increased by shear stress with magnitude- and time- dependent manner. 2) MMP-2 secretion was interrupted completely by shear stress, although the level of intracellular protein and mRNA expression of MMP-2 were unchanged. 3)Filipine, a sterol-binding protein which block the formation of caveola, inhibited MMP-2 secretion.
Conclusion : Our data suggests that laminar shear stress contribute to the formation of anti-atherosclerotic microenvironment in vessel wall through the regulation of type IV collagen metabolism of EC.
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