Cardiac role of cyclic-GMP hydrolyzing phosphodiesterase type 5: from experimental models to clinical trials.
Cyclic guanosine monophosphate (cGMP) and its primary signaling kinase, protein kinase G, play an important role in counterbalancing stress remodeling in the heart. Growing evidence supports a positive impact on a variety of cardiac disease conditions from the suppression of cGMP hydrolysis. The latter is regulated by members of the phosphodiesterase (PDE) superfamily, of which cGMP-selective PDE5 has been best studied. Inhibitors such as sildenafil and tadalafil ameliorate cardiac pressure and volume overload, ischemic injury, and cardiotoxicity. Clinical trials have begun exploring their potential to benefit dilated cardiomyopathy and heart failure with a preserved ejection fraction. This review discusses recent developments in the field, highlighting basic science and clinical studies.
Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Ross Building, Room 858, 720 Rutland Avenue, Baltimore, MD 21205, USA. dkass@jhmi.edu
David A
DA
Kass
D002243:Carbolines / Q000627:therapeutic use; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use; D050052:TRPC Cation Channels / Q000378:metabolism; D000068581:Tadalafil; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology
D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D050052:TRPC Cation Channels; D016212:Transforming Growth Factor beta; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D000242:Cyclic AMP; D017869:Cyclic GMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP