Abstract 15671: Direct Thrombin Inhibition with Dabigatran Attenuates Pressure Overload-Induced Cardiac Fibrosis and Diastolic Dysfunction in Mice

Introduction: Thrombin, a multifunctional serine protease, exerts proinflammatory and profibrotic cellular effects that may contribute to cardiac remodeling and hypertrophy mediated by its high-affinity protease-activated receptor-1 (PAR-1). The aim of the present study was to investigate whether direct thrombin inhibition with dabigatran attenuates myocardial injury in the setting of pressure overload-induced heart failure. Methods: Transverse aortic constriction (TAC) surgery was performed in C57/BL6J male mice (10-12 weeks old) to generate pressure overload and cardiac hypertrophy. TAC or sham mice were randomly assigned receive chow supplemented with dabigatran etexilate (10 mg/gm) or placebo (TAC+dabigatran, TAC+placebo, sham+dabigatran, sham+placebo). Results: Dabigatran treatment significantly extend thrombin clotting time by 3.2 fold (p Conclusion: Our results indicate that dabigatran attenuated cardiac fibrosis in the setting of pressure overload and improved diastolic function by inhibiting thrombin activity and possibly through down-regulation of PAR-1 expression without effects on cardiomyocyte hypertrophy.