Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis

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K S Russell1, D F Stern, P J Polverini

  • 1Division of Cardiovascular Medicine and Molecular Cardiobiology, Boyer Center for Molecular Medicine, New Haven, Connecticut, 06536-0812, USA.

The American Journal of Physiology
|December 22, 1999
PubMed

Insights

The ErbB receptor family plays a key role in vascular endothelial cells. Neuregulin-beta stimulation promotes endothelial cell proliferation and angiogenesis, independent of vascular endothelial growth factor.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • The ErbB (epidermal growth factor receptor) family are transmembrane tyrosine kinase receptors crucial for cell growth and signaling.
  • ErbB receptor-ligand interactions, specifically involving neuregulin, are implicated in vascular development.
  • Understanding ErbB signaling in endothelial cells is vital for vascular biology.

Purpose of the Study:

  • To investigate the expression of ErbB receptor family members in human umbilical vein endothelial cells (HUVEC).
  • To determine the functional effects of ErbB receptor stimulation in HUVEC.
  • To elucidate the role of ErbB signaling in endothelial cell function and angiogenesis.

Main Methods:

  • Investigated ErbB receptor expression patterns in HUVEC.
  • Stimulated HUVEC with neuregulin-beta, a known ErbB3/4 ligand.
  • Assessed downstream signaling events including calcium fluxes and receptor tyrosine phosphorylation.
  • Evaluated in vitro and in vivo angiogenic responses.

Main Results:

  • ErbB2, ErbB3, and ErbB4 were highly expressed in HUVEC, while ErbB1 (EGF-r) was undetectable.
  • Neuregulin-beta stimulation induced rapid calcium fluxes, receptor tyrosine phosphorylation, and HUVEC proliferation.
  • Neuregulin-beta elicited significant in vitro and in vivo angiogenic responses.
  • These angiogenic effects were independent of vascular endothelial cell growth factor (VEGF).

Conclusions:

  • The ErbB receptor family is actively involved in endothelial cell signaling.
  • Neuregulin-beta is a potent inducer of endothelial cell proliferation and angiogenesis.
  • ErbB signaling represents a significant pathway in vascular endothelial function and neovascularization.

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