Analysis of molecular pathogenesis of thrombosis in Japanese using mice with genetic mutations in anticoagulation/fibrinolytic factors

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461465
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: National Cardiovascular Center Research Institute
• 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)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• 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

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.

Free Research Field

血栓止血学