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Differential phosphodiesterase activity contributes to restrictive endothelial barrier function during angiogenesis
1Department of Anatomy, Cell Biology, and Injury Sciences, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
Microvascular Research
|October 27, 2001
Summary
Endothelial barrier function matures by day 5.0 in chick embryos, involving PDE III and IV inactivation. This leads to increased cAMP/PKA signaling and decreased cGMP/PKG pathway activity, enhancing vascular barrier properties.
Area of Science:
- Vascular biology
- Cell signaling
- Developmental biology
Background:
- Angiogenic endothelial hyperpermeability is a transient state during development.
- The chick chorioallantoic membrane model is used to study endothelial barrier function.
- Phosphodiesterase (PDE) enzymes regulate cyclic nucleotide signaling pathways.
Purpose of the Study:
- To investigate the role of phosphodiesterase (PDE) activity in the development of endothelial barrier function.
- To elucidate the signaling pathways involved in the maturation of angiogenic endothelial barrier function in vivo.
Main Methods:
- Inhibition of specific PDE isozymes (PDE I, III, IV) using selective inhibitors.
- Assessment of endothelial hyperpermeability using FITC-dextran extravasation.
- Evaluation of signaling pathways including cAMP/PKA and cGMP/PKG.
Main Results:
- Inhibition of PDE III and PDE IV at day 4.5 reduced hyperpermeability.
- Inhibition of cGMP-dependent pathways (PKG, soluble guanylate cyclase, nitric oxide synthase) also reduced hyperpermeability at day 4.5.
- Inhibition of cAMP-dependent protein kinase A (PKA) at day 5.0 impaired barrier function.
Conclusions:
- Endothelial barrier differentiation involves PDE III and IV inactivation.
- This inactivation leads to cAMP/PKA pathway activation and cGMP/PKG pathway downregulation.
- These signaling shifts are crucial for establishing a restrictive angiogenic endothelial barrier.
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