Cardiac Role of Cyclic-GMP Hydrolyzing Phosphodiesterase Type 5: From Experimental Models to Clinical Trials
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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.
KeywordsCyclic guanosine monophosphate Protein kinase G Cyclic GMP-dependent protein kinase Phosphodiesterase PDE5 PDE2 PDE1 Sildenafil Tadalafil Heart failure Hypertrophy Ventricular function Remodeling Fibrosis Transforming growth factor beta Cyclic AMP Signal transduction RGS2 TRPC channel Ischemia Preconditioning Mitochondria Human Genetic models
Dr. David Kass has received grants from the National Institutes of Health.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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