Tissue thrombin is associated with the pathogenesis of dilated cardiomyopathy
Autor: | Kosuke Minai, Taro Date, Ikuo Taniguchi, Makoto Kawai, Ichige Kajimura, Kazuo Ogawa, Junji Yajima, Haruka Kimura, Teiichi Yamane, Masahiro Ikegami, Akira Yoshii, Tomohisa Nagoshi, Satoshi Morimoto, Kenichi Hongo, Mamiko Owada, Yoichiro Kusakari, Toru Akaike, Susumu Minamisawa, Hiroshi Hano, Takuya Yoshino, Takayuki Ogawa, Seiichiro Matsuo, Michihiro Yoshimura, Daisuke Katoh, Sachio Morimoto, Yusuke Kashiwagi, Keiichi Ito |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cardiomyopathy Dilated medicine.medical_specialty Heart disease TNNT2 030204 cardiovascular system & hematology Pharmacology Antithrombins Dabigatran Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Thrombin Internal medicine medicine Animals Humans cardiovascular diseases business.industry Dilated cardiomyopathy musculoskeletal system medicine.disease Disease Models Animal 030104 developmental biology Direct thrombin inhibitor Case-Control Studies cardiovascular system Cardiology Cardiology and Cardiovascular Medicine Wound healing business medicine.drug |
Zdroj: | International journal of cardiology. 228 |
ISSN: | 1874-1754 |
Popis: | Background Thrombin is a serine protease known to be the final product of the coagulation cascade. However, thrombin plays other physiological roles in processes such as gastric contractions and vessel wound healing, and a state of coagulability is increased in patients with dilated cardiomyopathy (DCM). In this study, we investigate the role of thrombin in the pathogenesis of DCM. The purpose of this study is to clarify the role of thrombin in the pathogenesis of DCM and investigate the possibility of treatment against DCM by thrombin inhibition. Methods We investigated the expression of thrombin in the left ventricles of five patients with DCM who underwent the Batista operation and four patients without heart disease. Furthermore, 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 (∆K210 knock-in mouse) (B6;129- Tnnt2 tm2Mmto ) and assessed the effects of a direct thrombin inhibitor, dabigatran on ∆K210 knock-in mice using echocardiographic examinations, the Kaplan-Meier method and Western blotting. Results The immunohistochemical analysis showed a strong thrombin expression in the DCM patients compared to the patients without heart disease. In immunohistochemical analysis, a strong thrombin expression was observed in the heart tissues analysis in the ∆K210 knock-in mice. Dabigatran administration significantly improved fractional shortening according to the echocardiographic examination and the survival outcomes in ∆K210 knock-in mice. Conclusion Tissue thrombin is involved in the pathogenesis of DCM and thrombin inhibition can be beneficial for the treatment of DCM. |
Databáze: | OpenAIRE |
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