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Updated: Jan 27, 2026
Myocardial Infarction and Functional Outcome Assessment in Pigs
Published on: April 25, 2014
Rivaroxaban Suppresses the Progression of Ischemic Cardiomyopathy in a Murine Model of Diet-Induced Myocardial
Jingyi Liu1, Makoto Nishida1,2, Hiroyasu Inui1
1Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
Aim:
A direct oral anti-coagulant, FXa inhibitor, has been applied to the clinical treatment of myocardial infarction (MI). Experimental studies in mice indicated that FXa inhibitors reduced atherosclerosis and prevented cardiac dysfunction after coronary ligation. These studies suggested that protease-activated receptor (PAR) 2, a major receptor of activated FX, may play an important role in atherosclerosis and cardiac remodeling.
Methods:
The effects of a FXa inhibitor, rivaroxaban, were investigated in a new murine model of ischemic cardiomyopathy (ICM) using SR-BI KO/ApoeR61h/h mice (Hypo E mice) that developed MI by high-fat diet loading.
Results:
Hypo E mice were fed rivaroxaban-containing (n=49) or control chow diets (n=126) after the induction of MI. The survival curve of the rivaroxaban-treated group 2 weeks after the induction of MI was improved significantly as compared with the non-treatment group (survival rate: 75.5% vs. 47.4%, respectively, p=0.0012). Echocardiography and the expression of BNP showed that rivaroxaban attenuated heart failure. Histological analyses revealed that rivaroxaban reduced aortic atherosclerosis and coronary occlusion, and markedly attenuated cardiac fibrosis. Rivaroxaban treatment decreased cardiac PAR2 levels and pro-inflammatory genes. In vitro, rivaroxaban application demonstrated the increase of cell viability against hypoxia in cardiac myocytes and the reduction of hypoxia-induced inflammation and fibrosis-related molecules in cardiac fibroblasts. The effects of the PAR2 antagonist against hypoxia-induced inflammation were comparable to rivaroxaban in cardiac fibroblasts.
Conclusions:
Rivaroxaban treatment just after MI in Hypo E mice prevented the progression of ICM by attenuating cardiac remodeling, partially through the suppression of the PAR2-mediated inflammatory pathway.
Insights
Rivaroxaban, an FXa inhibitor, improved survival and attenuated cardiac remodeling in a mouse model of myocardial infarction (MI). This treatment reduced atherosclerosis and inflammation, partly by suppressing the PAR2 pathway.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Direct oral anticoagulants, specifically FXa inhibitors, are used clinically for myocardial infarction (MI).
- FXa inhibitors have shown potential in reducing atherosclerosis and preventing cardiac dysfunction in experimental models.
- Protease-activated receptor (PAR) 2, a receptor for activated FX, is implicated in atherosclerosis and cardiac remodeling.
Purpose of the Study:
- To investigate the effects of the FXa inhibitor rivaroxaban in a novel murine model of ischemic cardiomyopathy (ICM).
- To evaluate rivaroxaban's impact on atherosclerosis, cardiac remodeling, and survival following MI in this model.
Main Methods:
- A new murine model (SR-BI KO/ApoeR61h/h mice, or Hypo E mice) was developed to study ICM after MI induced by high-fat diet.
- Hypo E mice were treated with rivaroxaban or a control diet post-MI.
- Echocardiography, gene expression analysis (BNP), histological examination, and in vitro studies on cardiac myocytes and fibroblasts were performed.
Main Results:
- Rivaroxaban significantly improved survival rates in Hypo E mice post-MI (75.5% vs. 47.4%).
- Rivaroxaban treatment attenuated heart failure, reduced aortic atherosclerosis, coronary occlusion, and cardiac fibrosis.
- The drug decreased cardiac PAR2 levels and pro-inflammatory gene expression, and improved cardiac myocyte viability against hypoxia.
Conclusions:
- Rivaroxaban administered shortly after MI effectively prevented ICM progression in this murine model.
- The protective effects were attributed to the attenuation of cardiac remodeling, partly via suppression of the PAR2-mediated inflammatory pathway.
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