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Abnormalities in the Von Willebrand-Angiopoietin Axis Contribute to Dysregulated Angiogenesis and Angiodysplasia in

Carlo R Bartoli1,2, Samson Hennessy-Strahs1,2, Robert D Dowling3

  • 1Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

JACC. Basic to Translational Science
|March 29, 2021
PubMed

Insights

Children with Glenn circulation develop abnormal blood vessels. The study found issues with the von Willebrand factor (vWF)-angiopoietin axis, suggesting it may cause pulmonary arteriovenous malformations (AVMs) in these patients.

Area of Science:

  • Cardiovascular Science
  • Pediatric Cardiology
  • Angiogenesis Research

Background:

  • Children with bidirectional superior cavopulmonary (Glenn) circulation are prone to developing angiodysplasia and pulmonary arteriovenous malformations (AVMs).
  • The von Willebrand factor (vWF)-angiopoietin axis is implicated in AVM formation across various conditions.

Purpose of the Study:

  • To investigate the role of the vWF-angiopoietin axis in the development of pulmonary AVMs in children with Glenn circulation.
  • To compare angiogenic signaling, vWF metabolism, and angiopoietins between Glenn patients and controls, and between pulmonary and systemic circulations in Glenn patients.

Main Methods:

  • Analysis of global angiogenic signaling and vWF metabolism in children with Glenn circulation.
  • Measurement of angiopoietins levels.
  • Assessment of in vitro angiogenesis.

Main Results:

  • Derangements in global angiogenic signaling, vWF metabolism, and angiopoietins were observed in children with Glenn circulation compared to controls.
  • Significant differences were found in these markers between pulmonary and systemic circulations within Glenn patients.
  • In vitro angiogenesis assays revealed abnormalities.

Conclusions:

  • Abnormalities in the vWF-angiopoietin axis may contribute to the dysregulation of angiogenesis and the formation of pulmonary AVMs in Glenn circulation.
  • The vWF-angiopoietin axis represents a potential therapeutic target for correcting angiogenic imbalance in Glenn patients.
  • There is currently no targeted therapy for these AVMs, highlighting the need for further research and development.

Keywords:
ADAMTS-13, a disintegrin and metalloproteinase thrombospondin (motif) #13AVM, arteriovenous malformationEBM, endothelial basal mediaEGM, endothelial growth mediaGlennHUVEC, human umbilical vein endothelial cellIVC, inferior vena cavaLVAD, left ventricular assist devicePA, pulmonary arterySVC, superior vena cavaangiogenesisangiopoietinarteriovenous malformationvWF, von Willebrand factorvon Willebrand factor

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