title: Therapeutic potential of PDE modulation in treating heart disease.
abstract: Altered cyclic nucleotide-mediated signaling plays a critical role in the development of cardiovascular pathology. By degrading cAMP/cGMP, the action of cyclic nucleotide PDEs is essential for controlling cyclic nucleotide-mediated signaling intensity, duration, and specificity. Altered expression, localization and action of PDEs have all been implicated in causing changes in cyclic nucleotide signaling in cardiovascular disease. Accordingly, pharmacological inhibition of PDEs has gained interest as a treatment strategy and as an area of drug development. While targeting of certain PDEs has the potential to ameliorate cardiovascular disease, inhibition of others might actually worsen it. This review will highlight recent research on the physiopathological role of cyclic nucleotide signaling, especially with regard to PDEs. While the physiological roles and biochemical properties of cardiovascular PDEs will be summarized, the primary emphasis will be pathological. Research into the potential benefits and hazards of PDE inhibition will also be discussed.
authors.affiliation: Cardiovascular Research Institute, University of Rochester, 601 Elmwood Avenue, Box CVRI, Rochester, NY 14642, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: Knight
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods; D006331:Heart Diseases / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*
chemical_list: D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP
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