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Related Experiment Videos

Tissue factor deficiency causes cardiac fibrosis and left ventricular dysfunction.

R Pawlinski1, A Fernandes, B Kehrle

  • 1Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 12, 2002
PubMed
Summary

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Low levels of tissue factor (TF) in mice led to fatal hemorrhages and heart defects, suggesting TF is crucial for cardiac hemostasis and preventing heart damage.

Area of Science:

  • Cardiovascular Biology
  • Hemostasis and Thrombosis
  • Molecular Medicine

Background:

  • Tissue factor (TF) initiates coagulation via the extrinsic pathway (TF:FVIIa).
  • The intrinsic pathway involves Factor IXa (FIXa).
  • TF's role in cardiac hemostasis is not fully understood.

Purpose of the Study:

  • To investigate the role of tissue factor (TF) in cardiac hemostasis.
  • To determine the impact of reduced TF levels on cardiac function and lifespan.
  • To explore the potential of TF as a secondary hemostatic barrier in the heart.

Main Methods:

  • Generated mice with low levels of human TF (1% of wild-type) on an mTF(-/-) background.
  • Assessed lifespan, incidence of hemorrhage, and cardiac pathology in low-TF mice.

Related Experiment Videos

  • Measured left ventricular function using intracardiac methods.
  • Compared cardiac findings in low-TF, low-FVII, and FIX(-/-) mice.
  • Main Results:

    • Low-TF mice exhibited significantly shorter lifespans due to spontaneous fatal hemorrhages.
    • All low-TF mice developed cardiac defects, including hemosiderin deposition and fibrosis.
    • Left ventricular function was reduced by 30% in low-TF mice.
    • Similar cardiac pathology was observed in mice with low Factor VII (FVII) levels.
    • FIX(-/-) mice (hemophilia B model) had normal hearts, implicating TF and FVII, not FIX, in this cardiac phenotype.

    Conclusions:

    • Reduced TF levels impair cardiac hemostasis, leading to hemorrhage and fibrosis.
    • TF expression by cardiac myocytes may serve as a critical secondary hemostatic barrier.
    • Impaired hemostasis due to low TF or FVII causes cardiac damage, distinct from hemophilia B.