Protein kinase C activity contributes to endothelial hyperpermeability during early angiogenesis in the chick

L M Defouw1, D O Defouw

  • 1Department of Anatomy, Cell Biology and Injury Sciences, UMDNJ-New Jersey Medical School, Newark 07103, USA.

Tissue & Cell
|June 8, 2001
PubMed

Insights

Protein kinase C (PKC) activity contributes to leaky blood vessels during chick embryo development. Inhibiting PKC reduces leakage, while activating it can disrupt barrier function, suggesting PKC

Area of Science:

  • Developmental Biology
  • Vascular Biology
  • Cell Signaling

Background:

  • Angiogenesis in chick chorioallantoic membrane (CAM) involves microvascular proliferation.
  • Endothelial hyperpermeability characterizes neovascularization up to day 4.5, with barrier function developing by day 5.0.
  • The endogenous signaling pathways driving this transient hyperpermeability are not fully understood.

Purpose of the Study:

  • To investigate the role of protein kinase C (PKC) signaling in CAM endothelial barrier function.
  • To determine PKC's contribution to endothelial hyperpermeability during angiogenesis.
  • To correlate PKC activity with the development of restrictive barrier function.

Main Methods:

  • Utilized chick chorioallantoic membrane (CAM) model at embryonic days 4.5 and 5.0.
  • Assessed macromolecular extravasation using FITC-dextran 40.
  • Employed specific PKC inhibitors (calphostin C, bisindolymaleimide) and activators (PDD, PDBu).

Main Results:

  • Inhibition of PKC with calphostin C significantly reduced FITC-dextran 40 extravasation at day 4.5.
  • Selective PKC isoform inhibition also decreased extravasation, though to a lesser extent.
  • PKC activation at day 5.0 partially impaired barrier properties, increasing extravasation without gap formation.

Conclusions:

  • PKC activity is a contributing factor to endothelial hyperpermeability in the developing CAM vasculature.
  • Down-regulation of PKC signaling is temporally associated with the establishment of a restrictive endothelial barrier.
  • PKC represents a potential therapeutic target for modulating vascular permeability during angiogenesis.

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