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

Area of Science:

• Cardiovascular Biology
• Hemostasis and Thrombosis
• Cardiac Pathophysiology

Background:

• Activated factor X (FXa) is crucial for coagulation.
• Its role in pathological cardiac remodeling remains largely unknown.
• Hypertension-induced cardiac remodeling poses significant health risks.

Purpose of the Study:

• To investigate the direct role of cardiac-expressed activated factor X in pathological cardiac remodeling.
• To explore the therapeutic potential of inhibiting activated factor X in cardiac disease.

Main Methods:

• Utilized a mouse model of pressure overload-induced cardiac stress.
• Measured cardiac factor X mRNA expression and activity.
• Assessed cardiac hypertrophy, fibrosis, inflammation, and diastolic dysfunction.
• Conducted in vitro studies using cardiac myocytes and fibroblasts exposed to neurohormone stressors.
• Examined the effects of a low, coagulation-independent dose of rivaroxaban.

Main Results:

• Cardiac factor X expression and activity increased with pressure overload, correlating with cardiac hypertrophy, fibrosis, inflammation, and diastolic dysfunction.
• These detrimental cardiac changes were attenuated by rivaroxaban treatment.
• In vitro, neurohormone stressors upregulated activated factor X in cardiac cells.
• Activated factor X mediated protease-activated receptor signaling, promoting pro-hypertrophic and pro-fibrotic responses.

Conclusions:

• Cardiac-expressed activated factor X directly contributes to pathological cardiac remodeling.
• Inhibition of cardiac activated factor X presents a potential therapeutic strategy for hypertensive heart disease.
• Targeting activated factor X may offer a novel approach to prevent adverse cardiac remodeling.