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Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice

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 Res...

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Autores principales: Nakanishi, Nobuhiro, Kaikita, Koichi, Ishii, Masanobu, Oimatsu, Yu, Mitsuse, Tatsuro, Ito, Miwa, Yamanaga, Kenshi, Fujisue, Koichiro, Kanazawa, Hisanori, Sueta, Daisuke, Takashio, Seiji, Arima, Yuichiro, Araki, Satoshi, Nakamura, Taishi, Sakamoto, Kenji, Suzuki, Satoru, Yamamoto, Eiichiro, Soejima, Hirofumi, Tsujita, Kenichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japanese Circulation Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921351/
https://www.ncbi.nlm.nih.gov/pubmed/33693223
http://dx.doi.org/10.1253/circrep.CR-19-0117
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author Nakanishi, Nobuhiro
Kaikita, Koichi
Ishii, Masanobu
Oimatsu, Yu
Mitsuse, Tatsuro
Ito, Miwa
Yamanaga, Kenshi
Fujisue, Koichiro
Kanazawa, Hisanori
Sueta, Daisuke
Takashio, Seiji
Arima, Yuichiro
Araki, Satoshi
Nakamura, Taishi
Sakamoto, Kenji
Suzuki, Satoru
Yamamoto, Eiichiro
Soejima, Hirofumi
Tsujita, Kenichi
author_facet Nakanishi, Nobuhiro
Kaikita, Koichi
Ishii, Masanobu
Oimatsu, Yu
Mitsuse, Tatsuro
Ito, Miwa
Yamanaga, Kenshi
Fujisue, Koichiro
Kanazawa, Hisanori
Sueta, Daisuke
Takashio, Seiji
Arima, Yuichiro
Araki, Satoshi
Nakamura, Taishi
Sakamoto, Kenji
Suzuki, Satoru
Yamamoto, Eiichiro
Soejima, Hirofumi
Tsujita, Kenichi
author_sort Nakanishi, Nobuhiro
collection PubMed
description 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.
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spelling pubmed-79213512021-03-09 Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice Nakanishi, Nobuhiro Kaikita, Koichi Ishii, Masanobu Oimatsu, Yu Mitsuse, Tatsuro Ito, Miwa Yamanaga, Kenshi Fujisue, Koichiro Kanazawa, Hisanori Sueta, Daisuke Takashio, Seiji Arima, Yuichiro Araki, Satoshi Nakamura, Taishi Sakamoto, Kenji Suzuki, Satoru Yamamoto, Eiichiro Soejima, Hirofumi Tsujita, Kenichi Circ Rep Original article 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. The Japanese Circulation Society 2020-03-04 /pmc/articles/PMC7921351/ /pubmed/33693223 http://dx.doi.org/10.1253/circrep.CR-19-0117 Text en Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license.https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original article
Nakanishi, Nobuhiro
Kaikita, Koichi
Ishii, Masanobu
Oimatsu, Yu
Mitsuse, Tatsuro
Ito, Miwa
Yamanaga, Kenshi
Fujisue, Koichiro
Kanazawa, Hisanori
Sueta, Daisuke
Takashio, Seiji
Arima, Yuichiro
Araki, Satoshi
Nakamura, Taishi
Sakamoto, Kenji
Suzuki, Satoru
Yamamoto, Eiichiro
Soejima, Hirofumi
Tsujita, Kenichi
Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice
title Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice
title_full Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice
title_fullStr Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice
title_full_unstemmed Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice
title_short Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice
title_sort cardioprotective effects of rivaroxaban on cardiac remodeling after experimental myocardial infarction in mice
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921351/
https://www.ncbi.nlm.nih.gov/pubmed/33693223
http://dx.doi.org/10.1253/circrep.CR-19-0117
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