Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload.

•Factor X expression was increased in the heart following pressure overload and in isolated cardiac myocytes and fibroblasts.•Rivaroxaban treatment at doses that do not affect thrombin generation, blood coagulation or cardiac hemostasis attenuated cardiac inflammation, hypertrophy, and fibrosis caused by pressure overload and improved cardiac diastolic function.•Activated coagulation factor X induced PAR-1/-2–mediated elongated cardiomyocyte hypertrophy and PAR1-mediated cardiac fibroblast proliferation, migration and differentiation.•Activated coagulation factor X derived from a cardiac source may represent an important physiologic and pathophysiologic activator of PAR-1/PAR-2.•Non-anticoagulation dosage of rivaroxaban could provide an effective therapy to attenuate early phases of heart failure development.