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Molecular Pharmacology Fast Forward
First published on June 15, 2005; DOI: 10.1124/mol.105.015719

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Received for publication June 14, 2005.
Revised June 15, 2005.
Accepted for publication June 15, 2005.

The long and short of vascular smooth muscle phosphodiesterase-4 as a putative therapeutic target (Relates to Article by Tilley, et al. FastForward 3 June 2005)

Miles Houslay 1*

1 University of Glasgow

* Address correspondence to: E-mail: m.houslay{at}bio.gla.ac.uk

Abstract

In this issue Tilley and Maurice show that differentiation of vascular smooth muscle cells (VSMC) to a proliferative phenotype is associated with a profound up-regulation of specific phosphodiesterase-4 (PDE4) isoforms due to increased histone acetylation. The increased PDE4 activity is seen as preventing cAMP from inhibiting the enhanced proliferation, migration and production of intracellular matrix seen in activated VSMC. This perspective examines the proposal that selective inhibition of PDE4D1/2 could find use in adjunctive pharmacotherapy following percutaneous coronary interventions and, in addition, discusses the recent genetic evidence that PDE4D7 may provide a therapeutic target in stroke.


Key words: cAMP, Phosphodiesterases, Promoter analysis, Tissue hypertrophy


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