title: The long and short of vascular smooth muscle phosphodiesterase-4 as a putative therapeutic target.
abstract: In this issue, Tilley and Maurice (p. 596) show that differentiation of vascular smooth muscle cells to a proliferative phenotype is associated with a profound up-regulation of specific phosphodiesterase-4 (PDE4) isoforms because of increased histone acetylation. The increased PDE4 activity is seen as preventing cAMP from inhibiting the enhanced proliferation, migration, and production of extracellular matrix seen in activated VSMC. This Perspective examines the proposal that selective inhibition of PDE4D1/2 could find use in adjunctive pharmacotherapy after percutaneous coronary interventions and, in addition, discusses the recent genetic evidence that PDE4D7 may provide a therapeutic target in stroke.
authors.affiliation: Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, IBLS, Wolfson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK. m.houslay@bio.gla.ac.uk
authors.forename: Miles D
authors.initials: MD
authors.lastname: Houslay
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4