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

Abstract

It has been reported that combination therapies that include low-dose rivaroxaban seem to be effective in secondary prevention of acute coronary syndrome, 11 which suggests that rivaroxaban is effective not only for atrial fibrillation and venous thrombosis but also for coronary artery thrombosis. However, there is insufficient evidence about the cardioprotective effects of rivaroxaban on cardiac remodeling after MI. Rivaroxaban also exhibits anti-inflammatory properties, acting through amelioration of protease-activated receptor (PAR)-1 and-2 in arteriosclerosis models. 12-17 In addition, basic in vivo and in vitro research work has examined in detail the relationship between PARs and cardiac remod-C ardiac remodeling is an important prognostic factor in heart failure (HF). 1 Myocardial infarction (MI) is the most common cause of HF 2 and our understanding of the effect of cardiac remodeling in HF is based on MI studies. 3 The pathology of MI suggests that the inflammatory changes in the infarcted tissue correlate closely with cardiac function and prognosis after MI. 4,5 These findings suggest that modulation of the inflammatory response in the infarcted myocardium could potentially improve cardiac remodeling after MI. Rivaroxaban, an oral anticoagulant, is used to prevent and treat atrial fibrillation and venous thrombosis, because it exerts its anticoagulant properties by inhibiting activated

Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning

“…If commenced immediately after surgery or up to 24 hours thereafter, rivaroxaban applied in chow prevents intravascular thrombosis, improved cardiac systolic function, and decreased IS and inflammatory markers to variable extents. Within the infarct zone, levels of TNF α , tissue growth factor β , and both protease-activated receptors 1 and 2 are reportedly suppressed, while noninfarcted areas exhibit lower levels of atrial natriuretic peptide and NH 2 -terminal pro-B-type natriuretic peptide, activated ERK, and cardiomyocyte hypertrophy ( Bode et al, 2018 ; Nakanishi et al, 2020 ). Rivaroxaban also improved cardiac function and survival and suppressed transcription of IL-6 and collagens in a mouse model of secondary IRI prevention.…”

Rivaroxaban, a direct inhibitor of coagulation factor Xa, attenuates adverse cardiac remodeling in rats by regulating the PAR-2 and TGF-β1 signaling pathways

“…RIV has shown protective effects in a variety of mouse models. The study conducted by Nakanishi et al (2020) found that RIV protected against cardiac dysfunction by inhibiting PAR-1, PAR-2 and proinflammatory cytokines, with effects observed after seven days in MI model mice. Another study conducted by Bode et al (2018) showed that RIV did not reduce cardiac dysfunction in PAR-2 −/− mice.…”

Emerging topics on basic research in hypertension: interorgan communication and the need for interresearcher collaboration

“…Daci et al showed that pretreatment with rivaroxaban attenuated lipopolysaccharide (LPS)-induced acute vascular inflammation and contractile dysfunction in LPS-injected rats [ 41 ]. Nakanishi et al demonstrated that rivaroxaban protected against cardiac dysfunction after myocardial infarction in mice [ 42 ]. Reductions in protease-activated receptor (PAR)-1, PAR-2, and proinflammatory cytokines in the infarcted area were associated with the cardioprotective effects of rivaroxaban.…”