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Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis
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Published on: December 21, 2014

Alternatively spliced tissue factor induces angiogenesis through integrin ligation.

Y W van den Berg1, L G van den Hengel, H R Myers

  • 1The Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America
|October 31, 2009
PubMed
Summary

Alternatively spliced tissue factor (asTF) promotes angiogenesis by interacting with integrins, not through PAR-2 or Factor VIIa. This discovery offers a potential target for preventing pathological angiogenesis.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Full-length tissue factor (flTF) complexed with factor VIIa influences angiogenesis via PAR-2.
  • An alternatively spliced variant of TF (asTF) has a unique C terminus, replacing key domains.
  • Tumors from asTF-secreting cells show increased angiogenesis, but asTF's role is unclear.

Purpose of the Study:

  • To investigate how asTF regulates angiogenesis.
  • To determine the molecular pathways involved in asTF-mediated angiogenesis.

Main Methods:

  • Assessing angiogenesis in matrigel plugs and ex vivo models in mice.
  • Investigating the role of PAR-2, Factor VIIa, and integrins (alphaVbeta3, alpha6beta1) in asTF signaling.
  • Utilizing integrin blockade and TF-antibody to disrupt asTF-integrin interactions.

Main Results:

  • asTF significantly enhances angiogenesis, more so than soluble flTF.
  • asTF-induced angiogenesis is dose-dependent and independent of PAR-2 or VIIa.
  • asTF ligates integrins, leading to downstream signaling, including endothelial cell migration and capillary formation.
  • Aortic sprouting is sensitive to beta1 and beta3 integrin blockade and a specific TF-antibody.

Conclusions:

  • asTF promotes angiogenesis through integrin ligation, distinct from the PAR-dependent pathway of flTF.
  • asTF represents a novel target for therapeutic strategies aimed at inhibiting pathological angiogenesis.