1998 Fiscal Year Final Research Report Summary
Possible involvement of a mechanosensitive cell adhesion molecule PECAM-1 in the localization of atherosclerotic lesion.
| Project/Area Number |
09670250
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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 | National Cardiovascular Center Research Institute |
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Principal Investigator |
MASUDA Michitaka National Cardiovascular Center Research Institute, Department of Structural Analysis, Section Chief, 循環器形態部, 室長 (00190364)
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| Co-Investigator(Kenkyū-buntansha) |
KUSANO Kenichi National Cardiovascular Center Research Institute, Department of Structural Anal, 循環器形態部, 流動研究員
KANO Yumiko National Cardiovascular Center Research Institute, Department of Structural Anal, 循環器形態部, 室長 (30214498)
OSAWA Masaki National Cardiovascular Center Research Institute, Department of Structural Anal, 循環器形態部, 室員 (40291182)
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| Project Period (FY) |
1998 – 1999
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| Keywords | endothelial cell / blood vessel / atherosclerosis / PECAM-1 / tyrosine phosphorylation / SHP2 |
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| Research Abstract |
1. Functions of vascular endothelial cells are regulated by mechanical environments as well as by chemical environments. The mechanical environments or mechanical signals, such as fluid shear stress and tension, may play important roles in the initiation and the progression of vascular lesions and also in their recovery processes. For example, the localization of atherosclerotic lesion is known to be related by local hemodynamic force fields. This may be explained by changes in endothelial cell characters induced by fluid shear stress.
2. We have found that an cell-cell adhesion molecule, PECAM-l, is rapidly tyrosine phosphorylated by mechanical forces such as fluid shear stress and osmotic shocks. In the first year of this project, we found that the phosphorylated PECAM-l served a major plasma membrane anchoring site for a cytoplasmic protein tyrosine phosphatase, SH-PTP2 (SHP2, Syp). SH-PTP2 acts as a positive mediator in a MAP kinase (Erk) cascade. We are gathering evidence showing that the PECAM-l mediated mechanosignal transduction is involved in the Erk activation.
3. The Erk activation plays a major role in "slow" endothelial responses to flow including changes in gene expression. Our results provide biochemical bases for future analyses of "very slow" flow-modulated responses such as the initiation and the progression of atherosclerotic lesions.
4. We failed to detect the mechanosensitive PECAM-l tyrosine phosphorylation in various cell lines transfected with bovine PECAM-l except for human endothelial cells. This result suggests the presence of specific kinase(s) for PECAM-l in endothelial cells. Our current project is to identify the putative PECAM-l kinase(s).
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