2006 Fiscal Year Final Research Report Summary
Generating blood-flow-sensing-molecule-deficient mice and analysis of their physiological functions
| Project/Area Number |
16300149
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The University of Tokyo |
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Principal Investigator |
YAMAMOTO Kimiko The University of Tokyo, Graduate School of Medicine, lecturer, 大学院・医学系研究科, 講師 (00323618)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Joji The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20159528)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Shear Stress / Blood Flow / Mechanotransduction / Knockout mice / Endothelial Cells / Blood Vessels / P2X4 Receptor / Calcium Ion |
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| Research Abstract |
The structure and function of blood vessels adapt to environmental changes, for example, physical development and exercise. This phenomenon is based on the ability of the endothelial cells (ECs) to sense and respond to blood flow; however, its mechanism remains unclear. Here we show that ATP-gated P2X4 ion channel, expressed on ECs, is a key player in the mechanism. P2X4-deficient mice do not exhibit normal EC responses to flow, such as Ca^<2+> influx and subsequent production of nitric oxide (NO), a potent vasodilator. Additionally, vessel dilation induced by acute increases in blood flow is markedly suppressed in P2X4-deficient mice. Furthermore, P2X4-deficient mice have higher blood pressure and excrete smaller amounts of NO products in their urine than wild-type mice. Moreover, no adaptive vascular remodeling, i.e., decreases in vessel size in response to chronic decrease in blood flow, is observed in the P2X4-deficient mice. Thus, endothelial P2X4 channels are critical to the flow-sensitive mechanisms that regulate blood pressure and vascular remodeling.
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Research Products
(29 results)
