Phosphodiesterases and cyclic GMP regulation in heart muscle.

The cyclic nucleotide cGMP and its corresponding activated kinase cGK-1 serve as a counterbalance to acute and chronic myocardial stress. cGMP hydrolysis by several members of the phosphodiesterase (PDE) superfamily, PDE1, PDE2, and PDE5, regulate this signaling in the heart. This review details new insights regarding how these PDEs modulate cGMP and cGK-1 to influence heart function and chronic stress responses, and how their inhibition may provide potential therapeutic benefits.

[1]  F. Fedele,et al.  Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy: A Randomized, Controlled Clinical Trial Using Magnetic Resonance Imaging With Myocardial Tagging , 2012, Circulation.

[2]  Sang-Eun Lee,et al.  Long-Term Effects of Sildenafil in a Rat Model of Chronic Mitral Regurgitation: Benefits of Ventricular Remodeling and Exercise Capacity , 2012, Circulation.

[3]  S. Harding,et al.  Profiling of cAMP and cGMP phosphodiesterases in isolated ventricular cardiomyocytes from human hearts: comparison with rat and guinea pig. , 2012, Life sciences.

[4]  D. Kass,et al.  Preconditioning by Phosphodiesterase‐5 Inhibition Improves Therapeutic Efficacy of Adipose‐Derived Stem Cells Following Myocardial Infarction in Mice , 2012, Stem cells.

[5]  B. French,et al.  Differential Expression of PDE5 in Failing and Nonfailing Human Myocardium , 2012, Circulation. Heart failure.

[6]  W. Linke,et al.  Sildenafil and B-Type Natriuretic Peptide Acutely Phosphorylate Titin and Improve Diastolic Distensibility In Vivo , 2011, Circulation.

[7]  Clint L. Miller,et al.  Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart , 2011, Basic Research in Cardiology.

[8]  D. Kass,et al.  Phosphodiesterases and cardiac cGMP: evolving roles and controversies. , 2011, Trends in pharmacological sciences.

[9]  A. Abbate,et al.  Mitigation of the progression of heart failure with sildenafil involves inhibition of RhoA/Rho-kinase pathway. , 2011, American journal of physiology. Heart and circulatory physiology.

[10]  M. Zaccolo,et al.  cGMP Signals Modulate cAMP Levels in a Compartment-Specific Manner to Regulate Catecholamine-Dependent Signaling in Cardiac Myocytes , 2011, Circulation research.

[11]  J. Corbin,et al.  Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. , 2011, Physiological reviews.

[12]  M. Cheitlin.  PDE5 Inhibition With Sildenafil Improves Left Ventricular Diastolic Function, Cardiac Geometry, and Clinical Status in Patients With Stable Systolic Heart Failure: Results of a 1-Year, Prospective, Randomized, Placebo-Controlled Study , 2011 .

[13]  M. Cheitlin.  Long-Acting Phosphodiesterase-5 Inhibitor Tadalafil Attenuates Doxorubicin-Induced Cardiomyopathy without Interfering with Chemotherapeutic Effect , 2011 .

[14]  M. Movsesian,et al.  Phosphodiesterase inhibition in heart failure. , 2011, Handbook of experimental pharmacology.

[15]  Saisudha Koka,et al.  Attenuation of Doxorubicin-induced Cardiotoxicity by Tadalafil: A Long Acting Phosphodiesterase-5 Inhibitor. , 2010, Molecular and cellular pharmacology.

[16]  Dong I. Lee,et al.  Myocardial remodeling is controlled by myocyte-targeted gene regulation of phosphodiesterase type 5. , 2010, Journal of the American College of Cardiology.

[17]  N. Etienne-Selloum,et al.  Concerted Regulation of cGMP and cAMP Phosphodiesterases in Early Cardiac Hypertrophy Induced by Angiotensin II , 2010, PloS one.

[18]  R. Fischmeister,et al.  Feedback Control Through cGMP-Dependent Protein Kinase Contributes to Differential Regulation and Compartmentation of cGMP in Rat Cardiac Myocytes , 2010, Circulation research.

[19]  S. Francis.  The role of cGMP-dependent protein kinase in controlling cardiomyocyte cGMP. , 2010, Circulation research.

[20]  J. Beavo,et al.  Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy , 2010, Proceedings of the National Academy of Sciences.

[21]  H. Ke,et al.  Conformation Changes, N-terminal Involvement, and cGMP Signal Relay in the Phosphodiesterase-5 GAF Domain* , 2010, The Journal of Biological Chemistry.

[22]  D. Kass,et al.  TRP-ing up Heart and Vessels: Canonical Transient Receptor Potential Channels and Cardiovascular Disease , 2010, Journal of cardiovascular translational research.

[23]  Clint L. Miller,et al.  Targeting Cyclic Nucleotide Phosphodiesterase in the Heart: Therapeutic Implications , 2010, Journal of cardiovascular translational research.

[24]  M. Shattock,et al.  Phospholemman Ser69 phosphorylation contributes to sildenafil-induced cardioprotection against reperfusion injury , 2010, American journal of physiology. Heart and circulatory physiology.

[25]  Xinli Hu,et al.  Oxidative Stress Regulates Left Ventricular PDE5 Expression in the Failing Heart , 2010, Circulation.

[26]  D. Kass,et al.  Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation Novel mechanism of cardiac stress modulation by PDE5 inhibition. , 2010, Journal of molecular and cellular cardiology.

[27]  M. Nishida,et al.  Phosphorylation of TRPC6 Channels at Thr69 Is Required for Anti-hypertrophic Effects of Phosphodiesterase 5 Inhibition* , 2010, The Journal of Biological Chemistry.

[28]  Dong I. Lee,et al.  PDE5A suppression of acute β-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation , 2010, Basic Research in Cardiology.

[29]  J. Pandit,et al.  Cyclic nucleotide binding GAF domains from phosphodiesterases: structural and mechanistic insights. , 2009, Structure.

[30]  A. Wojtovich,et al.  Role of Ca 2 (cid:1) /Calmodulin–Stimulated Cyclic Nucleotide Phosphodiesterase 1 in Mediating Cardiomyocyte Hypertrophy , 2009 .

[31]  K. Fennell,et al.  Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct , 2009, Proceedings of the National Academy of Sciences.

[32]  R. Arena,et al.  The impact of pharmacotherapy on the cardiopulmonary exercise test response in patients with heart failure: a mini review. , 2009, Current vascular pharmacology.

[33]  J. Corbin,et al.  cGMP-Hydrolytic Activity and Its Inhibition by Sildenafil in Normal and Failing Human and Mouse Myocardium , 2009, Journal of Pharmacology and Experimental Therapeutics.

[34]  Mark J. Kohr,et al.  Phosphodiesterase 5 restricts NOS3/Soluble guanylate cyclase signaling to L-type Ca2+ current in cardiac myocytes. , 2009, Journal of molecular and cellular cardiology.

[35]  D. Kass,et al.  Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. , 2009, Pharmacology & therapeutics.

[36]  D. Kass,et al.  Pressure-overload magnitude-dependence of the anti-hypertrophic efficacy of PDE5A inhibition. , 2009, Journal of molecular and cellular cardiology.

[37]  W. Linke,et al.  Titin-based mechanical signalling in normal and failing myocardium. , 2009, Journal of molecular and cellular cardiology.

[38]  H. Milting,et al.  Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling. , 2009, Cardiovascular research.

[39]  Lei Xi,et al.  ERK phosphorylation mediates sildenafil-induced myocardial protection against ischemia-reperfusion injury in mice. , 2009, American journal of physiology. Heart and circulatory physiology.

[40]  K. Sipido,et al.  Ventricular Phosphodiesterase-5 Expression Is Increased in Patients With Advanced Heart Failure and Contributes to Adverse Ventricular Remodeling After Myocardial Infarction in Mice , 2009, Circulation.

[41]  D. Kass,et al.  Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. , 2009, Journal of the American College of Cardiology.

[42]  D. Kass,et al.  Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice. , 2009, The Journal of clinical investigation.

[43]  D. Kass,et al.  Phosphodiesterase 5 inhibition blocks pressure overload-induced cardiac hypertrophy independent of the calcineurin pathway. , 2008, Cardiovascular research.

[44]  Christian Andresen,et al.  Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs , 2008, Circulation research.

[45]  Daniel Morton,et al.  Immunohistochemical Localization of Phosphodiesterase 2A in Multiple Mammalian Species , 2006, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[46]  J. Nielsen-Kudsk,et al.  Effects of phosphodiesterase‐5 inhibition by sildenafil in the pressure overloaded right heart , 2008, European journal of heart failure.

[47]  D. Kass,et al.  Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes. , 2008, Cellular signalling.

[48]  Anindita Das,et al.  Protein Kinase G-dependent Cardioprotective Mechanism of Phosphodiesterase-5 Inhibition Involves Phosphorylation of ERK and GSK3β* , 2008, Journal of Biological Chemistry.

[49]  D. Thedens,et al.  Sarcolemma-localized nNOS is required to maintain activity after mild exercise , 2008, Nature.

[50]  D. Kass,et al.  Sustained Soluble Guanylate Cyclase Stimulation Offsets Nitric-Oxide Synthase Inhibition to Restore Acute Cardiac Modulation by Sildenafil , 2008, Journal of Pharmacology and Experimental Therapeutics.

[51]  K. Nakao,et al.  Regulator of G-Protein Signaling Subtype 4 Mediates Antihypertrophic Effect of Locally Secreted Natriuretic Peptides in the Heart , 2008, Circulation.

[52]  F. Vandeput,et al.  Cyclic Nucleotide Phosphodiesterase PDE1C1 in Human Cardiac Myocytes* , 2007, Journal of Biological Chemistry.

[53]  R. Gerszten,et al.  Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension , 2007 .

[54]  A. Hatzelmann,et al.  Characterization of inhibitors of phosphodiesterase 1C on a human cellular system , 2007, The FEBS journal.

[55]  P. Light,et al.  Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility , 2007, Circulation.

[56]  Manuela Zaccolo,et al.  of in The Role of the in the A Molecular for Generating cAMP and cGMP Signaling Cross-Talk Role of Phosphodiesterases and Implications for Cardiac Pathophysiology , 2007 .

[57]  D. Kass,et al.  Compartmentalization of Cardiac &bgr;-Adrenergic Inotropy Modulation by Phosphodiesterase Type 5 , 2007 .

[58]  A. Bender,et al.  Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterases , 2006 .

[59]  John McAnally,et al.  TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. , 2006, The Journal of clinical investigation.

[60]  J. Beavo,et al.  Cyclic Nucleotide Phosphodiesterases: Molecular Regulation to Clinical Use , 2006, Pharmacological Reviews.

[61]  D. Cooper,et al.  Cyclic Guanosine Monophosphate Compartmentation in Rat Cardiac Myocytes , 2006, Circulation.

[62]  D. Nagel,et al.  Role of Nuclear Ca2+/Calmodulin-Stimulated Phosphodiesterase 1A in Vascular Smooth Muscle Cell Growth and Survival , 2006, Circulation research.

[63]  C. Lugnier.  Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. , 2006, Pharmacology & therapeutics.

[64]  M. Zaccolo,et al.  Compartmentalized Phosphodiesterase-2 Activity Blunts &bgr;-Adrenergic Cardiac Inotropy via an NO/cGMP-Dependent Pathway , 2006, Circulation research.

[65]  D. Nagel,et al.  Role of Nuclear Ca 2 (cid:1) /Calmodulin-Stimulated Phosphodiesterase 1A in Vascular Smooth Muscle Cell Growth and Survival , 2006 .

[66]  D. Kass,et al.  Sildenafil Inhibits β-Adrenergic–Stimulated Cardiac Contractility in Humans , 2005 .

[67]  R. Fischmeister,et al.  Species- and tissue-dependent effects of NO and cyclic GMP on cardiac ion channels. , 2005, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[68]  P. Fisher,et al.  Phosphodiesterase-5 Inhibition With Sildenafil Attenuates Cardiomyocyte Apoptosis and Left Ventricular Dysfunction in a Chronic Model of Doxorubicin Cardiotoxicity , 2005, Circulation.

[69]  Anindita Das,et al.  Phosphodiesterase-5 Inhibitor Sildenafil Preconditions Adult Cardiac Myocytes against Necrosis and Apoptosis , 2005, Journal of Biological Chemistry.

[70]  P. Fisher,et al.  Pharmacological preconditioning with sildenafil: Basic mechanisms and clinical implications. , 2005, Vascular pharmacology.

[71]  R. Zoraghi,et al.  Structural and Functional Features in Human PDE5A1 Regulatory Domain That Provide for Allosteric cGMP Binding, Dimerization, and Regulation* , 2005, Journal of Biological Chemistry.

[72]  J. Beavo,et al.  Crystal structure of the tandem GAF domains from a cyanobacterial adenylyl cyclase: modes of ligand binding and dimerization. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[73]  D. Kass,et al.  Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy , 2005, Nature Medicine.

[74]  M. Zaccolo,et al.  cGMP Catabolism by Phosphodiesterase 5A Regulates Cardiac Adrenergic Stimulation by NOS3-Dependent Mechanism , 2004, Circulation research.

[75]  D. Kass,et al.  Sildenafil inhibits beta-adrenergic-stimulated cardiac contractility in humans. , 2005, Circulation.

[76]  A. Y. Wu,et al.  Molecular Determinants for Cyclic Nucleotide Binding to the Regulatory Domains of Phosphodiesterase 2A* , 2004, Journal of Biological Chemistry.

[77]  J. Beavo,et al.  Regulation of Nitric Oxide–Sensitive Guanylyl Cyclase Cyclic GMP Phosphodiesterases and Regulation of Smooth Muscle Function Structure, Regulation, and Function of Membrane Guanylyl Cyclase Receptors, With a Focus on GC-A Cyclic GMP–Dependent Protein Kinases and the Cardiovascular System: Insights F , 2003 .

[78]  S. Balaji,et al.  Modeling and mutational analysis of the GAF domain of the cGMP‐binding, cGMP‐specific phosphodiesterase, PDE5 , 2003, FEBS letters.

[79]  A. Monfort,et al.  Identification and distribution of different mRNA variants produced by differential splicing in the human phosphodiesterase 9A gene. , 2003, Biochemical and biophysical research communications.

[80]  P. Ferdinandy,et al.  Effect of classic preconditioning on the gene expression pattern of rat hearts: a DNA microarray study , 2003, FEBS letters.

[81]  J. Beavo,et al.  PDE5 is converted to an activated state upon cGMP binding to the GAF A domain , 2003, The EMBO journal.

[82]  J. Corbin,et al.  Sildenafil citrate does not affect cardiac contractility in human or dog heart , 2003, Current medical research and opinion.

[83]  K. Omori,et al.  cGMP-Phosphodiesterase Activity Is Up-regulated in Response to Pressure Overload of Rat Ventricles , 2003, Bioscience, biotechnology, and biochemistry.

[84]  A. Y. Wu,et al.  The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[85]  P. Greengard,et al.  Phosphodiesterase 1B Knock-Out Mice Exhibit Exaggerated Locomotor Hyperactivity and DARPP-32 Phosphorylation in Response to Dopamine Agonists and Display Impaired Spatial Learning , 2002, The Journal of Neuroscience.

[86]  J. Beavo,et al.  Cyclic Nucleotide Phosphodiesterase 1C Promotes Human Arterial Smooth Muscle Cell Proliferation , 2002, Circulation research.

[87]  J. Beavo,et al.  Upregulation of Phosphodiesterase 1A1 Expression Is Associated With the Development of Nitrate Tolerance , 2001, Circulation.

[88]  D. Kass,et al.  Cardiac phosphodiesterase 5 (cGMP‐specific) modulates β‐adrenergic signaling in vivo and is down‐regulated in heart failure , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[89]  R. Fischmeister,et al.  Cyclic GMP regulation of the L‐type Ca2+ channel current in human atrial myocytes , 2001, The Journal of physiology.

[90]  A. Wilderspin,et al.  Cloning of dog heart PDE1A - a first detailed characterization at the molecular level in this species. , 2001, Gene.

[91]  G. D. Thomas,et al.  Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[92]  J. Corbin,et al.  Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. , 2000, European journal of biochemistry.

[93]  J. Corbin,et al.  Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. , 1999, The American journal of cardiology.

[94]  K. Ferguson,et al.  Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase. , 1997, Gene.

[95]  K. Sadhu,et al.  Isolation and Characterization of cDNAs Corresponding to Two Human Calcium, Calmodulin-regulated, 3′,5′-Cyclic Nucleotide Phosphodiesterases (*) , 1996, The Journal of Biological Chemistry.

[96]  W. K. Sonnenburg,et al.  Identification of Inhibitory and Calmodulin-binding Domains of the PDE1A1 and PDE1A2 Calmodulin-stimulated Cyclic Nucleotide Phosphodiesterases (*) , 1995, The Journal of Biological Chemistry.

[97]  W. K. Sonnenburg,et al.  Molecular cloning of a cDNA encoding the "61-kDa" calmodulin-stimulated cyclic nucleotide phosphodiesterase. Tissue-specific expression of structurally related isoforms. , 1993, The Journal of biological chemistry.

[98]  C. Lugnier,et al.  Selective inhibition of cyclic nucleotide phosphodiesterases of human, bovine and rat aorta. , 1986, Biochemical pharmacology.

[99]  R. Sharma,et al.  Differential regulation of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase isoenzymes by cyclic AMP-dependent protein kinase and calmodulin-dependent phosphatase. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[100]  P. Hamet,et al.  Characteristics of a new binding protein distinct from the kinase for guanosine 3':5'-monophosphate in rat platelets. , 1980, Biochimica et biophysica acta.

[101]  T. Lincoln,et al.  Characterization of a novel cGMP binding protein from rat lung. , 1980, The Journal of biological chemistry.

[102]  J. Beavo,et al.  Stimulation of adenosine 3',5'-monophosphate hydrolysis by guanosine 3',5'-monophosphate. , 1971, The Journal of biological chemistry.