| Project/Area Number |
25461465
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Banno Fumiaki 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (00373514)
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| Co-Investigator(Kenkyū-buntansha) |
AKIYAMA MASASHI 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30298179)
MIYATA TOSHIYUKI 国立研究開発法人国立循環器病研究センター, 病院, シニア研究員 (90183970)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | プロテインS / プラスミノーゲン / ノックインマウス / 遺伝子変異 / 日本人の血栓症 |
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| Outline of Final Research Achievements |
The K196E mutation in protein S (PS) is a genetic risk factor for venous thromboembolism (VTE) with a prevalence of ~2% within the Japanese population. The A620T mutation in plasminogen (Plg), originally identified in a VTE patient, is present in ~4% of the Japanese population. We generated PS-K196E mice, PS-deficient mice and Plg-A622T mice. In this study, we analyzed their venous thrombotic states, comparing with mice carrying the factor V (FV) R504Q mutation, a genetic risk for VTE in Caucasians. A deep vein thrombosis model and two pulmonary embolism model experiments revealed that PS-K196E mice, PS-deficient mice and FV-R504Q mice were much more susceptible to VTE compared with wild-type mice, supporting a causal relationship between the PS-K196E mutation and VTE. However, experimental models of VTE showed largely similar phenotypes in Plg-A622T mice and wild-type mice. Hence, our results showed that the Plg-A620T mutation does not increase the risk of VTE.
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