The Investigation of Tissue Thrombin

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860589
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Ito Keiichi 東京慈恵会医科大学, 医学部, 助教 (70646843)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 拡張型心筋症 / トロンビン

Outline of Final Research Achievements

Thrombin is a serine protease known to be the final product of the coagulation cascade. A state of coagulability is increased in patients with dilated cardiomyopathy (DCM). The purpose of this study is to investigate the role of thrombin in the pathogenesis of DCM. We investigated the involvement of thrombin in the development of DCM using knock-in mice with a deletion mutation of cardiac troponin T that causes human DCM (DCM mouse)(B6;129-Tnnt2 tm2Mmto) and assessed the effects of a direct thrombin inhibitor, dabigatran on DCM mice. Dabigatran administration significantly improved fractional shortening according to the echocardiographic examination and the survival outcomes. In addition, a strong thrombin expression was observed in the heart tissues on the Western blot analysis in the ∆K210 knock-in mice. In conclusion, tissue thrombin is involved in the pathogenesis of DCM and thrombin inhibition can be benefical for the treatment of DCM.

Free Research Field

循環器内科学