Factor Xa Inhibition with Apixaban Does Not Influence Cardiac Remodelling in Rats with Heart Failure After Myocardial Infarction
Open Access
- 26 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cardiovascular Drugs and Therapy
- Vol. 35 (5), 953-963
- https://doi.org/10.1007/s10557-020-06999-7
Abstract
Background Heart failure (HF) is considered to be a prothrombotic condition and it has been suggested that coagulation factors contribute to maladaptive cardiac remodelling via activation of the protease-activated receptor 1 (PAR1). We tested the hypothesis that anticoagulation with the factor Xa (FXa) inhibitor apixaban would ameliorate cardiac remodelling in rats with HF after myocardial infarction (MI). Methods and Results Male Sprague-Dawley rats were either subjected to permanent ligation of the left ascending coronary artery (MI) or sham surgery. The MI and sham animals were randomly allocated to treatment with placebo or apixaban in the chow (150 mg/kg/day), starting 2 weeks after surgery. Cardiac function was assessed using echocardiography and histological and molecular markers of cardiac hypertrophy were assessed in the left ventricle (LV). Apixaban resulted in a fivefold increase in anti-FXa activity compared with vehicle, but no overt bleeding was observed and haematocrit levels remained similar in apixaban- and vehicle-treated groups. After 10 weeks of treatment, LV ejection fraction was 42 ± 3% in the MI group treated with apixaban and 37 ± 2 in the vehicle-treated MI group (p > 0.05). Both vehicle- and apixaban-treated MI groups also displayed similar degrees of LV dilatation, LV hypertrophy and interstitial fibrosis. Histological and molecular markers for pathological remodelling were also comparable between groups, as was the activity of signalling pathways downstream of the PAR1 receptor. Conclusion FXa inhibition with apixaban does not influence pathological cardiac remodelling after MI. These data do not support the use of FXa inhibitor in HF patients with the aim to amend the severity of HF. Graphical AbstractKeywords
Funding Information
- Indonesia Endowment Fund for Education (LPDP No. 20150722083422)
- Hartstichting (CVON DOSIS, grant 2014-40, CVON SHE-PREDICTS-HF, grant 2017-21, and CVON RED-CVD, grant 2017-11)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO VIDI, grant 917.13.350, NWO VENI, grant 016.176.147)
This publication has 57 references indexed in Scilit:
- Increased SRF transcriptional activity in human and mouse skeletal muscle is a signature of insulin resistanceJCI Insight, 2011
- Protease-Activated Receptor-1 Contributes to Cardiac Remodeling and HypertrophyCirculation, 2007
- Myocardial infarct size measurement in the mouse chronic infarction model: comparison of area- and length-based approachesJournal of Applied Physiology, 2007
- p38 Kinase rescues failing myocardium after myocardial infarction: evidence for angiogenic and anti‐apoptotic mechanismsThe FASEB Journal, 2006
- Survival kinases in ischemic preconditioning and postconditioningCardiovascular Research, 2006
- Protease-activated receptor and endothelial-myocyte uncoupling in chronic heart failureAmerican Journal of Physiology-Heart and Circulatory Physiology, 2005
- Risk Factors for Deep Vein Thrombosis in Inpatients Aged 65 and Older: A Case‐Control Multicenter StudyJournal of the American Geriatrics Society, 2004
- Protease-Activated Receptor-1–Mediated DNA Synthesis in Cardiac Fibroblast Is via Epidermal Growth Factor Receptor TransactivationCirculation Research, 2002
- The Phosphoinositide 3-Kinase PathwayScience, 2002
- Congestive heart failure and outpatient risk of venous thromboembolism A retrospective, case-control studyJournal of Clinical Epidemiology, 2001