Increased phosphodiesterase 3A/4B expression after angioplasty and the effect on VASP phosphorylation.

The beneficial effects of coronary angioplasty are limited by the proliferation and migration of vascular smooth muscle cells leading to restenosis. We hypothesized that increased activity of phosphodiesterase (PDE) after angioplasty in response to growth factors such as platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF), leads to reduced cAMP levels, which, in turn, may contribute to vascular smooth muscle cell proliferation. In rats subjected to angioplasty, aortic expression and activity of PDE3/PDE4 were increased within 24 h and associated with reduced phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a substrate for cAMP-dependent protein kinase A (PKA).

Differential effects of phosphodiesterase PDE-3/PDE-4-specific inhibitors on vasoconstriction and cAMP-dependent vasorelaxation following balloon angioplasty.

It is known that cAMP and cGMP are important for vasorelaxation, and cyclic nucleotide phosphodiesterases (PDEs) regulate their levels. Balloon angioplasty (BAL) is associated with reduced cAMP and cGMP levels, and inhibition of PDE-3 reduces restenosis. In this study, we found that BAL increased PDE-3 activity, which affected vasoreactivity of rat aortic rings 24-h post-BAL; these were compared with intact (INT) and ex vivo endothelium-denuded rings (RUB) from sham rats.