Journal
JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 5, Issue 1, Pages 69-83Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2019.10.006
Keywords
activated coagulation factor X; cardiac hypertrophy; coagulation; fibrosis; protease-activated receptors; rivaroxaban
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Activated factor X is a key component of the coagulation cascade, but whether it directly regulates pathological cardiac remodeling is unclear. In mice subjected to pressure overload stress, cardiac factor X mRNA expression and activity increased concurrently with cardiac hypertrophy, fibrosis, inflammation and diastolic dysfunction, and responses blocked with a low coagulation-independent dose of rivaroxaban. In vitro, neurohormone stressors increased activated factor X expression in both cardiac myocytes and fibroblasts, resulting in activated factor Xmediated activation of protease-activated receptors and pro-hypertrophic and -fibrotic responses, respectively. Thus, inhibition of cardiac-expressed activated factor X could provide an effective therapy for the prevention of adverse cardiac remodeling in hypertensive patients. (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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