Direct Thrombin Inhibitors Prevent Left Atrial Remodeling Associated With Heart Failure in Rats
| Autor: | Jumeau, Céline, Rupin, Alain, Chieng-Yane, Pauline, Mougenot, Nathalie, Zahr, Noël, David-Dufilho, Monique, Hatem, Stéphane N. |
|---|---|
| Přispěvatelé: | Institut de Recherches Internationales Servier [Suresnes] (IRIS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), FRS Consulting, Phénotypage du petit animal (UMS28), Université Pierre et Marie Curie - Paris 6 (UPMC), CIC Paris Est, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the Servier Research Institute and Laboratories, (contract n°122694/BR/VO), the Agence Nationale de la Recherche (ANR), Paris (National program 'Investissements d'avenir': ANR-10-IAHU-05), and the European Network for Translational Research in AF (FP7 EUTRAF- 261057 and H2020CATCH-ME 633196). Dr. Jumeau received a CIFRE grant from the French Ministry of Education and Research, Paris (2012-0374)., ANR-10-IAHU-0005,ICAN,Institut de Cardiologie-Métabolisme-Nutrition(2010), European Project: 261057,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EUTRAF(2010), European Project: 633196,H2020,H2020-PHC-2014-two-stage,CATCH ME(2015), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Administateur, HAL Sorbonne Université, Instituts Hospitalo-Universitaires - Institut de Cardiologie-Métabolisme-Nutrition - - ICAN2010 - ANR-10-IAHU-0005 - IAHU - VALID, The European Network for Translational Research in Atrial Fibrillation - EUTRAF - - EC:FP7:HEALTH2010-11-01 - 2015-10-31 - 261057 - VALID, Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly - CATCH ME - - H20202015-05-01 - 2019-04-30 - 633196 - VALID |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
lcsh:Diseases of the circulatory (Cardiovascular) system medicine.medical_specialty AF atrial fibrillation medicine.drug_class heart failure atrial arrhythmia 030204 cardiovascular system & hematology CTGF connective tissue growth factor 03 medical and health sciences 0302 clinical medicine Thrombin [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Fibrosis Internal medicine medicine ANP atrial natriuretic peptide NFATc3 nuclear factor of activated T cells 3 direct thrombin inhibitor remodeling DTI direct thrombin inhibitor BNP brain natriuretic peptide business.industry Anticoagulant anticoagulant Pre-Clinical Research Atrial fibrillation medicine.disease [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system 3. Good health CTGF 030104 developmental biology lcsh:RC666-701 Direct thrombin inhibitor Heart failure Cardiology MI myocardial infarction PAR protease-activated receptor PAI plasminogen activator inhibitor Cardiology and Cardiovascular Medicine business MHC myosin heavy chain medicine.drug Discovery and development of direct thrombin inhibitors |
| Zdroj: | Jacc. Basic to Translational Science JACC: Basic to Translational Science JACC : Basic to Translational Science JACC : Basic to Translational Science, Elsevier on behalf of the American College of Cardiology Foundation, 2016, 1 (5), ⟨10.1016/j.jacbts.2016.05.002⟩ JACC : Basic to Translational Science, 2016, 1 (5), ⟨10.1016/j.jacbts.2016.05.002⟩ JACC: Basic to Translational Science, Vol 1, Iss 5, Pp 328-339 (2016) |
| ISSN: | 2452-302X |
| DOI: | 10.1016/j.jacbts.2016.05.002⟩ |
| Popis: | Summary 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. Visual Abstract Highlights • Oral direct anticoagulants such as DTIs, but not vitamin K antagonist, diminish the progression of atrial dilation associated with heart failure in a rat model. • Prevention of atrial dilation by DTI is associated with decreased duration of atrial arrhythmia induced by burst pacing. • DTI inhibits interstitial fibrosis, extracellular matrix remodeling, and hypertrophy of atrial myocardium. • Plasma DTI concentrations inhibiting atrial remodeling are lower than those required for therapeutic anticoagulant activity. • DTIs may be of interest to prevent the progression of atrial fibrillation substrate in addition to their anticoagulant activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|