著者

Nobuhiro Nakanishi Koichi Kaikita Masanobu Ishii Yu Oimatsu Tatsuro Mitsuse Miwa Ito Kenshi Yamanaga Koichiro Fujisue Hisanori Kanazawa Daisuke Sueta Seiji Takashio Yuichiro Arima Satoshi Araki Taishi Nakamura Kenji Sakamoto Satoru Suzuki Eiichiro Yamamoto Hirofumi Soejima Kenichi Tsujita

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

vol.2, no.3, pp.158-166, 2020-03-10 (Released:2020-03-10)

参考文献数

51

被引用文献数

10

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Background:Direct-activated factor X (FXa) plays an important role in thrombosis and is also involved in inflammation via the protease-activated receptor (PAR)-1 and PAR-2 pathway. We hypothesized that rivaroxaban protects against cardiac remodeling after myocardial infarction (MI).Methods and Results:MI was induced in wild-type mice by permanent ligation of the left anterior descending coronary artery. At day 1 after MI, mice were randomly assigned to the rivaroxaban and vehicle groups. Mice in the rivaroxaban group were provided with a regular chow diet plus rivaroxaban. We evaluated cardiac function by echocardiography, pathology, expression of mRNA and protein at day 7 after MI. Rivaroxaban significantly improved cardiac systolic function, decreased infarct size and cardiac mass compared with the vehicle. Rivaroxaban also downregulated the mRNA expression levels of tumor necrosis factor-α, transforming growth factor-β, PAR-1 and PAR-2 in the infarcted area, and both A-type and B-type natriuretic peptides in the non-infarcted area compared with the vehicle. Furthermore, rivaroxaban attenuated cardiomyocyte hypertrophy and the phosphorylation of extracellular signal-regulated kinase in the non-infarcted area compared with the vehicle.Conclusions:Rivaroxaban protected against cardiac dysfunction in MI model mice. Reduction of PAR-1, PAR-2 and proinflammatory cytokines in the infarcted area may be involved in its cardioprotective effects.