title: Direct Thrombin Inhibitors Prevent Left Atrial Remodeling Associated With Heart Failure in Rats.
abstract: The present study tested the hypothesis that thrombin participates in formation of left atrial remodeling and that direct oral anticoagulants, such as direct thrombin inhibitors (DTIs), can prevent its progression. In a rat model of heart failure associated with left atrial dilation, we found that chronic treatment with DTIs reduces the atrial remodeling and the duration of atrial fibrillation (AF) episodes induced by burst pacing by inhibiting myocardial hypertrophy and fibrosis. In addition to the prevention of thromboembolism complicating AF, DTIs may be of interest to slow down the progression of the arrhythmogenic substrate.
authors.affiliation: Sorbonne University, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche 1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Servier Research Institute, Suresnes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Jumeau
authors.affiliation: Servier Research Institute, Suresnes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Rupin
authors.affiliation: FRS Consulting, Paris, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Chieng-Yane
authors.affiliation: Inserm-Sorbonnes-Universités, Unité Mixte de Service 28 Université Pierre et Marie Curie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mougenot
authors.affiliation: INSERM Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Department of Pharmacology and Centre d'Investigation Clinique 1421, Paris, France.
authors.forename: Noël
authors.initials: N
authors.lastname: Zahr
authors.affiliation: Sorbonne University, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche 1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: David-Dufilho
authors.affiliation: Sorbonne University, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche 1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Cardiology Department, ICAN, Paris, France.
authors.forename: Stéphane N
authors.initials: SN
authors.lastname: Hatem
keywords: AF, atrial fibrillation; ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; CTGF, connective tissue growth factor; DTI, direct thrombin inhibitor; MHC, myosin heavy chain; MI, myocardial infarction; NFATc3, nuclear factor of activated T cells 3; PAI, plasminogen activator inhibitor; PAR, protease-activated receptor; anticoagulant; atrial arrhythmia; direct thrombin inhibitor; heart failure; remodeling