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

• Published in: JACC. Basic to translational science Vol. 5; no. 1; pp. 69 - 83
• Main Authors: Guo, Xinji, Kolpakov, Mikhail A, Hooshdaran, Bahman, Schappell, William, Wang, Tao, Eguchi, Satoru, Elliott, Katherine J, Tilley, Douglas G, Rao, A Koneti, Andrade-Gordon, Patricia, Bunce, Matthew, Madhu, Chintala, Houser, Steven R, Sabri, Abdelkarim
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01-01-2020
• Subjects: PRECLINICAL RESEARCH; FXa, activated coagulation factor X; protease-activated receptors; TAC, transverse aortic constriction; aPTT, activated partial thromboplastin time; PT, prothrombin time; rivaroxaban; coagulation; activated coagulation factor X; HF, heart failure; PAR, protease-activated receptor; PO, pressure-overload; fibrosis; cardiac hypertrophy
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2019.10.006

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 X-mediated 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.