An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases

References

• Bender AT, Beavo JA. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev. 2006 Sep;58(3):488–520.
   PubMed Web of Science ®Google Scholar
• Guellich A, Mehel H, Fischmeister R. Cyclic AMP synthesis and hydrolysis in the normal and failing heart. Pflugers Arch. 2014 Jun;466(6):1163–1175.
   PubMed Web of Science ®Google Scholar
• Beavo J, Francis SH, Houslay MD. Cyclic nucleotide phosphodiesterases in health and disease. Boca Raton: CRC Press/Taylor & Francis; 2007.
   Google Scholar
• Liu S, Li Y, Kim S, et al. Phosphodiesterases coordinate cAMP propagation induced by two stimulatory G protein-coupled receptors in hearts. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6578–6583.
   PubMed Web of Science ®Google Scholar
• Lohse MJ, Engelhardt S, Eschenhagen T. What is the role of beta-adrenergic signaling in heart failure? Circ Res. 2003;93(10):896–906.
   PubMed Web of Science ®Google Scholar
• Feldman DS, Elton TS, Sun B, et al. Mechanisms of disease: detrimental adrenergic signaling in acute decompensated heart failure. Nat Clin Pract Cardiovasc Med. 2008 Apr;5(4):208–218.
   PubMedGoogle Scholar
• Peart JN, Headrick JP. Adenosinergic cardioprotection: multiple receptors, multiple pathways. Pharmacol Ther. 2007 May;114(2):208–221.
   PubMed Web of Science ®Google Scholar
• Szentmiklosi AJ, Cseppento A, Harmati G, et al. Novel trends in the treatment of cardiovascular disorders: site- and event- selective adenosinergic drugs. Curr Med Chem. 2011;18(8):1164–1187.
   PubMed Web of Science ®Google Scholar
• Okumura S, Takagi G, Kawabe J, et al. Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload. Proc Natl Acad Sci U S A. 2003;100(17):9986–9990.
   PubMed Web of Science ®Google Scholar
• Okumura S, Vatner DE, Kurotani R, et al. Disruption of type 5 adenylyl cyclase enhances desensitization of cyclic adenosine monophosphate signal and increases Akt signal with chronic catecholamine stress. Circulation. 2007 Oct 16;116(16):1776–1783.
   PubMed Web of Science ®Google Scholar
• Takahashi T, Tang T, Lai NC, et al. Increased cardiac adenylyl cyclase expression is associated with increased survival after myocardial infarction. Circulation. 2006 Aug 1;114(5):388–396.
   PubMed Web of Science ®Google Scholar
• Tang T, Gao MH, Lai NC, et al. Adenylyl cyclase type 6 deletion decreases left ventricular function via impaired calcium handling. Circulation. 2008 Jan 1;117(1):61–69.
   PubMed Web of Science ®Google Scholar
• Knight WE, Chen S, Zhang Y, et al. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction. Proc Natl Acad Sci U S A. 2016 Oct 20;113(45):E7116–E7125.
   Web of Science ®Google Scholar
• Zhang Y, Knight W, Chen S, et al. Multiprotein complex with TRPC (transient receptor potential-canonical) Channel, PDE1C (phosphodiesterase 1C), and A2R (adenosine A2 receptor) plays a critical role in regulating cardiomyocyte cAMP and survival. Circulation. 2018 Oct 30;138(18):1988–2002.
   PubMed Web of Science ®Google Scholar
• Ding B, Abe J, Wei H, et al. Functional role of phosphodiesterase 3 in cardiomyocyte apoptosis: implication in heart failure. Circulation. 2005 May 17;111(19):2469–2476.
   PubMed Web of Science ®Google Scholar
• Tajima M, Bartunek J, Weinberg EO, et al. Atrial natriuretic peptide has different effects on contractility and intracellular pH in normal and hypertrophied myocytes from pressure-overloaded hearts. Circulation. 1998 Dec 15;98(24):2760–2764.
   PubMed Web of Science ®Google Scholar
• Ohte N, Cheng CP, Suzuki M, et al. Effects of atrial natriuretic peptide on left ventricular performance in conscious dogs before and after pacing-induced heart failure. J Pharmacol Exp Ther. 1999 Nov;291(2):589–595.
   PubMed Web of Science ®Google Scholar
• Shah AM, MacCarthy PA. Paracrine and autocrine effects of nitric oxide on myocardial function. Pharmacol Ther. 2000 Apr;86(1):49–86.
   PubMed Web of Science ®Google Scholar
• Pierkes M, Gambaryan S, Boknik P, et al. Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A-deficient mice. Cardiovasc Res. 2002 Mar;53(4):852–861.
   PubMed Web of Science ®Google Scholar
• Su J, Zhang Q, Moalem J, et al. Functional effects of C-type natriuretic peptide and nitric oxide are attenuated in hypertrophic myocytes from pressure-overloaded mouse hearts. Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1367–73.
   PubMed Web of Science ®Google Scholar
• Hammond J, Balligand JL. Nitric oxide synthase and cyclic GMP signaling in cardiac myocytes: from contractility to remodeling. J Mol Cell Cardiol. 2012 Feb;52(2):330–340.
   PubMed Web of Science ®Google Scholar
• Bice JS, Burley DS, Baxter GF. Novel approaches and opportunities for cardioprotective signaling through 3ʹ,5ʹ-cyclic guanosine monophosphate manipulation. J Cardiovasc Pharmacol Ther. 2014 May;19(3):269–282.
   PubMed Web of Science ®Google Scholar
• Su J, Scholz PM, Weiss HR. Differential effects of cGMP produced by soluble and particulate guanylyl cyclase on mouse ventricular myocytes. Exp Biol Med (Maywood). 2005 Apr;230(4):242–250.
   PubMed Web of Science ®Google Scholar
• Fischmeister R, Castro LR, Abi-Gerges A, et al. Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases. Circ Res. 2006 Oct 13;99(8):816–828.
   PubMed Web of Science ®Google Scholar
• Zaccolo M, Di Benedetto G, Lissandron V, et al. Restricted diffusion of a freely diffusible second messenger: mechanisms underlying compartmentalized cAMP signalling. Biochem Soc Trans. 2006 Aug;34(Pt 4):495–497.
   PubMedGoogle Scholar
• Stangherlin A, Zaccolo M. Phosphodiesterases and subcellular compartmentalized cAMP signaling in the cardiovascular system. Am J Physiol Heart Circ Physiol. 2012 Jan;302(2):H379–90.
   PubMed Web of Science ®Google Scholar
• Lomas O, Zaccolo M. Phosphodiesterases maintain signaling fidelity via compartmentalization of cyclic nucleotides. Physiology (Bethesda). 2014 Mar;29(2):141–149.
   PubMed Web of Science ®Google Scholar
• Brescia M, Zaccolo M. Modulation of compartmentalised cyclic nucleotide signalling via local inhibition of phosphodiesterase activity. Int J Mol Sci. 2016 2;17(10):Oct. .
   Web of Science ®Google Scholar
• Schleicher K, Zaccolo M. Using cAMP sensors to study cardiac nanodomains. J Cardiovasc Dev Dis. 2018 Mar 13;5(1):17.
   PubMed Web of Science ®Google Scholar
• Chao YC, Surdo NC, Pantano S, et al. Imaging cAMP nanodomains in the heart. Biochem Soc Trans. 2019 Oct 31;47(5):1383–1392.
   PubMedGoogle Scholar
• Bork NI, Nikolaev VO. cGMP signaling in the cardiovascular system-the role of compartmentation and its live cell imaging. Int J Mol Sci. 2018 Mar 10;19(3). DOI:https://doi.org/10.3390/ijms19030801
   Google Scholar
• Miller CL, Oikawa M, Cai Y, et al. Role of Ca2+/calmodulin-stimulated cyclic nucleotide phosphodiesterase 1 in mediating cardiomyocyte hypertrophy. Circ Res. 2009 Nov 6;105(10):956–964.
   PubMed Web of Science ®Google Scholar
• Knight WE, Chen S, Zhang Y, et al. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction. Proc Natl Acad Sci U S A. 2016 Nov 8;113(45):E7116–E7125.
   PubMed Web of Science ®Google Scholar
• Zoccarato A, Surdo NC, Aronsen JM, et al. Cardiac hypertrophy is inhibited by a local pool of cAMP regulated by phosphodiesterase 2. Circ Res. 2015 Sep 25;117(8):707–719.
   PubMed Web of Science ®Google Scholar
• Ding B, Abe JI, Wei H, et al. Functional role of phosphodiesterase 3 in cardiomyocyte apoptosis: implication in heart failure. Circulation. 2005 May 17;111(19):2469–2476.
   PubMed Web of Science ®Google Scholar
• Lehnart SE, Wehrens XH, Reiken S, et al. Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell. 2005 Oct 7;123(1):25–35.
   PubMed Web of Science ®Google Scholar
• Nagendran J, Archer SL, Soliman D, et al. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007 Jul 17;116(3):238–248.
   PubMed Web of Science ®Google Scholar
• Patrucco E, Albergine MS, Santana LF, et al. Phosphodiesterase 8A (PDE8A) regulates excitation-contraction coupling in ventricular myocytes. J Mol Cell Cardiol. 2010 Aug;49(2):330–333.
   PubMed Web of Science ®Google Scholar
• Lee DI, Zhu G, Sasaki T, et al. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature. 2015 Mar 26;519(7544):472–476.
   PubMed Web of Science ®Google Scholar
• Chen S, Zhang Y, Lighthouse JK, et al. A novel role of cyclic nucleotide phosphodiesterase 10A in pathological cardiac remodeling and dysfunction. Circulation. 2020 Jan 21;141(3):217–233.
   PubMed Web of Science ®Google Scholar
• Shakur Y, Holst LS, Landstrom TR, et al. Regulation and function of the cyclic nucleotide phosphodiesterase (PDE3) gene family. Prog Nucleic Acid Res Mol Biol. 2001;66:241–277.
   PubMed Web of Science ®Google Scholar
• Movsesian M. Novel approaches to targeting PDE3 in cardiovascular disease. Pharmacol Ther. 2016 Jul;163:74–81.
   PubMed Web of Science ®Google Scholar
• Maurice DH, Palmer D, Tilley DG, et al. Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system. Mol Pharmacol. 2003;64(3):533–546.
   PubMed Web of Science ®Google Scholar
• Fujishige K, Kotera J, Michibata H, et al. Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J Biol Chem. 1999 Jun 25;274(26):18438–18445.
   PubMed Web of Science ®Google Scholar
• Loughney K, Snyder PB, Uher L, et al. Isolation and characterization of PDE10A, a novel human 3ʹ, 5ʹ-cyclic nucleotide phosphodiesterase. Gene. 1999 Jun 24;234(1):109–117.
   PubMed Web of Science ®Google Scholar
• Soderling SH, Bayuga SJ, Beavo JA. Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):7071–7076.
   PubMed Web of Science ®Google Scholar
• Charych EI, Jiang LX, Lo F, et al. Interplay of palmitoylation and phosphorylation in the trafficking and localization of phosphodiesterase 10A: implications for the treatment of schizophrenia. J Neurosci. 2010 Jul 7;30(27):9027–9037.
   PubMed Web of Science ®Google Scholar
• Russwurm C, Koesling D, Russwurm M. Phosphodiesterase 10A is tethered to a synaptic signaling complex in striatum. J Biol Chem. 2015 May 8;290(19):11936–11947.
   PubMed Web of Science ®Google Scholar
• Gross-Langenhoff M, Hofbauer K, Weber J, et al. cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10 and cGMP for the tandem GAF domain of phosphodiesterase 11. J Biol Chem. 2006 Feb 3;281(5):2841–2846.
   PubMed Web of Science ®Google Scholar
• Houslay MD, Baillie GS, Maurice DH. cAMP-Specific phosphodiesterase-4 enzymes in the cardiovascular system: a molecular toolbox for generating compartmentalized cAMP signaling. Circ Res. 2007 Apr 13;100(7):950–966.
   PubMed Web of Science ®Google Scholar
• Xie M, Blackman B, Scheitrum C, et al. The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases (PDE4s). Biochem J. 2014 May 1;459(3):539–550.
   PubMedGoogle Scholar
• Wang P, Wu P, Egan RW, et al. Human phosphodiesterase 8A splice variants: cloning, gene organization, and tissue distribution. Gene. 2001 Dec 12;280(1–2):183–194.
   PubMed Web of Science ®Google Scholar
• Soderling SH, Bayuga SJ, Beavo JA. Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase. Proc Natl Acad Sci U S A. 1998;95(15):8991–8996.
   PubMed Web of Science ®Google Scholar
• Hayashi M, Shimada Y, Nishimura Y, et al. Genomic organization, chromosomal localization, and alternative splicing of the human phosphodiesterase 8B gene. Biochem Biophys Res Commun. 2002 Oct 11;297(5):1253–1258.
   PubMed Web of Science ®Google Scholar
• Kass DA, Champion HC, Beavo JA. Phosphodiesterase type 5: expanding roles in cardiovascular regulation. Circ Res. 2007Nov26;101(11):1084–1095.
   PubMed Web of Science ®Google Scholar
• Francis S, Zoraghi R, Kotera J, et al. Phosphodiesterase-5: molecular characteristics relating to structure, function, and regulation. In: Cyclic nucleotide phosphodiesterases in health and disease. Boca Raton: CRC; 2006. p. 131.
   Google Scholar
• Fisher DA, Smith JF, Pillar JS, et al. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. J Biol Chem. 1998;273(25):15559–15564.
   PubMed Web of Science ®Google Scholar
• Rentero C, Monfort A, Puigdomenech P. Identification and distribution of different mRNA variants produced by differential splicing in the human phosphodiesterase 9A gene. Biochem Biophys Res Commun. 2003 Feb 14;301(3):686–692.
   PubMed Web of Science ®Google Scholar
• Vandeput F, Wolda SL, Krall J, et al. Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes. J Biol Chem. 2007 Nov 9;282(45):32749–32757.
   PubMed Web of Science ®Google Scholar
• Chen S, Knight WE, Yan C. Roles of PDE1 in pathological cardiac remodeling and dysfunction. J Cardiovasc Dev Dis. 2018Apr23;5(2):22.
   Web of Science ®Google Scholar
• Miller CL, Cai Y, Oikawa M, et al. Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart. Basic Res Cardiol. 2011 Nov;106(6):1023–1039.
   PubMed Web of Science ®Google Scholar
• Wu MP, Zhang YS, Xu X, et al. Vinpocetine attenuates pathological cardiac remodeling by inhibiting cardiac hypertrophy and fibrosis. Cardiovasc Drugs Ther. 2017 Apr;31(2):157–166.
   PubMed Web of Science ®Google Scholar
• Hashimoto T, Kim GE, Tunin RS, et al. Acute enhancement of cardiac function by phosphodiesterase type 1 inhibition. Circulation. 2018 Oct 30;138(18):1974–1987.
   PubMed Web of Science ®Google Scholar
• Stephenson DT, Coskran TM, Wilhelms MB, et al. Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species. J Histochem Cytochem. 2009 Oct;57(10):933–949.
   PubMed Web of Science ®Google Scholar
• Mehel H, Emons J, Vettel C, et al. Phosphodiesterase-2 is up-regulated in human failing hearts and blunts beta-adrenergic responses in cardiomyocytes. J Am Coll Cardiol. 2013 Oct 22;62(17):1596–1606.
   PubMed Web of Science ®Google Scholar
• Baliga RS, Preedy MEJ, Dukinfield MS, et al. Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure. Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):E7428–E7437.
   PubMed Web of Science ®Google Scholar
• Vettel C, Lammle S, Ewens S, et al. PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways. Am J Physiol Heart Circ Physiol. 2014 Apr 15;306(8):H1246–52.
   PubMed Web of Science ®Google Scholar
• Hartzell HC, Fischmeister R. Opposite effects of cyclic GMP and cyclic AMP on Ca2+ current in single heart cells. Nature. 1986 Sep 18-24;323(6085):273–275.
   PubMed Web of Science ®Google Scholar
• Vandecasteele G, Verde I, Rucker-Martin C, et al. Cyclic GMP regulation of the L-type Ca(2+) channel current in human atrial myocytes. J Physiol. 2001;533(Pt 2):329–340.
   PubMed Web of Science ®Google Scholar
• Soler F, Fernandez-Belda F, Perez-Schindler J, et al. PDE2 activity differs in right and left rat ventricular myocardium and differentially regulates beta2 adrenoceptor-mediated effects. Exp Biol Med (Maywood). 2015 Sep;240(9):1205–1213.
   PubMed Web of Science ®Google Scholar
• Mongillo M, Tocchetti CG, Terrin A, et al. Compartmentalized phosphodiesterase-2 activity blunts beta-adrenergic cardiac inotropy via an NO/cGMP-dependent pathway. Circ Res. 2006 Feb 3;98(2):226–234.
   PubMed Web of Science ®Google Scholar
• Monterisi S, Lobo MJ, Livie C, et al. PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling. Elife. 2017 May 2;6:e21374.
   Web of Science ®Google Scholar
• Vettel C, Lindner M, Dewenter M, et al. Phosphodiesterase 2 protects against catecholamine-induced arrhythmia and preserves contractile function after myocardial infarction. Circ Res. 2017 Jan 6;120(1):120–132.
   PubMed Web of Science ®Google Scholar
• Surapisitchat J, Jeon KI, Yan C, et al. Differential regulation of endothelial cell permeability by cGMP via phosphodiesterases 2 and 3. Circ Res. 2007 Oct 12;101(8):811–818.
   PubMed Web of Science ®Google Scholar
• Chung YW, Lagranha C, Chen Y, et al. Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury. Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2253–62.
   PubMed Web of Science ®Google Scholar
• Ding B, Abe J, Wei H, et al. A positive feedback loop of phosphodiesterase 3 (PDE3) and inducible cAMP early repressor (ICER) leads to cardiomyocyte apoptosis. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14771–14776.
   PubMed Web of Science ®Google Scholar
• Yan C, Ding B, Shishido T, et al. Activation of extracellular signal-regulated kinase 5 reduces cardiac apoptosis and dysfunction via inhibition of a phosphodiesterase 3A/inducible cAMP early repressor feedback loop. Circ Res. 2007 Mar 2;100(4):510–519.
   PubMed Web of Science ®Google Scholar
• Smith CJ, Huang R, Sun D, et al. Development of decompensated dilated cardiomyopathy is associated with decreased gene expression and activity of the milrinone-sensitive cAMP phosphodiesterase PDE3A. Circulation. 1997;96(9):3116–3123.
   PubMed Web of Science ®Google Scholar
• Sato N, Asai K, Okumura S, et al. Mechanisms of desensitization to a PDE inhibitor (milrinone) in conscious dogs with heart failure. Am J Physiol. 1999;276(5 Pt 2):H1699–705.
   PubMedGoogle Scholar
• Abi-Gerges A, Richter W, Lefebvre F, et al. Decreased expression and activity of cAMP phosphodiesterases in cardiac hypertrophy and its impact on beta-adrenergic cAMP signals. Circ Res. 2009 Oct 9;105(8):784–792.
   PubMed Web of Science ®Google Scholar
• Takahashi K, Osanai T, Nakano T, et al. Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure. Heart Vessels. 2002 Sep;16(6):249–256.
   PubMed Web of Science ®Google Scholar
• Knollmann BC, Knollmann-Ritschel BE, Weissman NJ, et al. Remodelling of ionic currents in hypertrophied and failing hearts of transgenic mice overexpressing calsequestrin. J Physiol. 2000 Jun 1;525(Pt 2):483–498.
   PubMed Web of Science ®Google Scholar
• Tse J, Brackett NL, Kuo JF. Alterations in activities of cyclic nucleotide systems and in beta-adrenergic receptor-mediated activation of cyclic AMP-dependent protein kinase during progression and regression of isoproterenol-induced cardiac hypertrophy. Biochim Biophys Acta. 1978 Sep 6;542(3):399–411.
   PubMedGoogle Scholar
• Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 1991;325(21):1468–1475.
   PubMed Web of Science ®Google Scholar
• Sun B, Li H, Shakur Y, et al. Role of phosphodiesterase type 3A and 3B in regulating platelet and cardiac function using subtype-selective knockout mice. Cell Signal. 2007 Aug;19(8):1765–1771.
   PubMed Web of Science ®Google Scholar
• Beca S, Ahmad F, Shen W, et al. Phosphodiesterase type 3A regulates basal myocardial contractility through interacting with sarcoplasmic reticulum calcium ATPase type 2a signaling complexes in mouse heart. Circ Res. 2013 Jan 18;112(2):289–297.
   PubMed Web of Science ®Google Scholar
• Ahmad F, Shen W, Vandeput F, et al. Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2. J Biol Chem. 2015 Mar 13;290(11):6763–6776.
   PubMed Web of Science ®Google Scholar
• Oikawa M, Wu M, Lim S, et al. Cyclic nucleotide phosphodiesterase 3A1 protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol. 2013 Nov;64:11–19.
   PubMed Web of Science ®Google Scholar
• Woo CH, Le NT, Shishido T, et al. Novel role of C terminus of Hsc70-interacting protein (CHIP) ubiquitin ligase on inhibiting cardiac apoptosis and dysfunction via regulating ERK5-mediated degradation of inducible cAMP early repressor. Faseb J. 2010 Dec;24(12):4917–4928.
   PubMed Web of Science ®Google Scholar
• Iwaya S, Oikawa M, Chen Y, et al. Phosphodiesterase 3A1 protects the heart against angiotensin II-induced cardiac remodeling through regulation of transforming growth factor-beta expression. Int Heart J. 2014;55(2):165–168.
   PubMed Web of Science ®Google Scholar
• Polidovitch N, Yang S, Sun H, et al. Phosphodiesterase type 3A (PDE3A), but not type 3B (PDE3B), contributes to the adverse cardiac remodeling induced by pressure overload. J Mol Cell Cardiol. 2019 Jul;132:60–70.
   PubMed Web of Science ®Google Scholar
• Richter W, Xie M, Scheitrum C, et al. Conserved expression and functions of PDE4 in rodent and human heart. Basic Res Cardiol. 2011 Mar;106(2):249–262.
   PubMed Web of Science ®Google Scholar
• Kostic MM, Erdogan S, Rena G, et al. Altered expression of PDE1 and PDE4 cyclic nucleotide phosphodiesterase isoforms in 7-oxo-prostacyclin-preconditioned rat heart. J Mol Cell Cardiol. 1997;29(11):3135–3146.
   PubMed Web of Science ®Google Scholar
• Karam S, Margaria JP, Bourcier A, et al. Cardiac overexpression of PDE4B blunts beta-adrenergic response and maladaptive remodeling in heart failure. Circulation. 2020 Apr 8;142(2):161–174.
   PubMed Web of Science ®Google Scholar
• Bobin P, Varin A, Lefebvre F, et al. Calmodulin kinase II inhibition limits the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors. Cardiovasc Res. 2016 May 1;110(1):151–161.
   PubMed Web of Science ®Google Scholar
• Fertig BA, Baillie GS. PDE4-Mediated cAMP Signalling. J Cardiovasc Dev Dis. 2018 Jan 31;5(1):8.
   PubMed Web of Science ®Google Scholar
• Leroy J, Richter W, Mika D, et al. Phosphodiesterase 4B in the cardiac L-type Ca(2)(+) channel complex regulates Ca(2)(+) current and protects against ventricular arrhythmias in mice. J Clin Invest. 2011 Jul;121(7):2651–2661.
   PubMed Web of Science ®Google Scholar
• Beca S, Helli PB, Simpson JA, et al. Phosphodiesterase 4D regulates baseline sarcoplasmic reticulum Ca2+ release and cardiac contractility, independently of L-type Ca2+ current. Circ Res. 2011 Oct 14;109(9):1024–1030.
   PubMed Web of Science ®Google Scholar
• Sin YY, Edwards HV, Li X, et al. Disruption of the cyclic AMP phosphodiesterase-4 (PDE4)-HSP20 complex attenuates the beta-agonist induced hypertrophic response in cardiac myocytes. J Mol Cell Cardiol. 2011 May;50(5):872–883.
   PubMed Web of Science ®Google Scholar
• Edwards HV, Scott JD, Baillie GS. PKA phosphorylation of the small heat-shock protein Hsp20 enhances its cardioprotective effects. Biochem Soc Trans. 2012 Feb;40(1):210–214.
   PubMedGoogle Scholar
• Martin TP, Hortigon-Vinagre MP, Findlay JE, et al. Targeted disruption of the heat shock protein 20-phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy. FEBS Open Bio. 2014;4:923–927.
   PubMed Web of Science ®Google Scholar
• Dodge KL, Khouangsathiene S, Kapiloff MS, et al. mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. Embo J. 2001 Apr 17;20(8):1921–1930.
   PubMed Web of Science ®Google Scholar
• Dodge-Kafka KL, Soughayer J, Pare GC, et al. The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways. Nature. 2005 Sep 22;437(7058):574–578.
   PubMed Web of Science ®Google Scholar
• Wang L, Burmeister BT, Johnson KR, et al. UCR1C is a novel activator of phosphodiesterase 4 (PDE4) long isoforms and attenuates cardiomyocyte hypertrophy. Cell Signal. 2015 May;27(5):908–922.
   PubMed Web of Science ®Google Scholar
• Corbin J, Rannels S, Neal D, et al. Sildenafil citrate does not affect cardiac contractility in human or dog heart. Curr Med Res Opin. 2003;19(8):747–752.
   PubMed Web of Science ®Google Scholar
• Vandeput F, Krall J, Ockaili R, et al. cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium. J Pharmacol Exp Ther. 2009 Sep;330(3):884–891.
   PubMed Web of Science ®Google Scholar
• Pokreisz P, Vandenwijngaert S, Bito V, 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. Circulation. 2009 Jan 27;119(3):408–416.
   PubMed Web of Science ®Google Scholar
• Zhang M, Koitabashi N, Nagayama T, et al. Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes. Cell Signal. 2008 Aug 26;20(12):2231–2236.
   Web of Science ®Google Scholar
• Lu Z, Xu X, Hu X, et al. Oxidative stress regulates left ventricular PDE5 expression in the failing heart. Circulation. 2010 Apr 6;121(13):1474–1483.
   PubMed Web of Science ®Google Scholar
• Takimoto E, Champion HC, Belardi D, et al. cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circ Res. 2005 Jan 7;96(1):100–109.
   PubMed Web of Science ®Google Scholar
• Lukowski R, Rybalkin SD, Loga F, et al. Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes. Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5646–5651.
   PubMed Web of Science ®Google Scholar
• Borlaug BA, Melenovsky V, Marhin T, et al. Sildenafil inhibits beta-adrenergic-stimulated cardiac contractility in humans. Circulation. 2005 Oct 25;112(17):2642–2649.
   PubMed Web of Science ®Google Scholar
• Takimoto E, Belardi D, Tocchetti CG, et al. Compartmentalization of cardiac beta-adrenergic inotropy modulation by phosphodiesterase type 5. Circulation. 2007 Apr 24;115(16):2159–2167.
   PubMed Web of Science ®Google Scholar
• Senzaki H, Smith CJ, Juang GJ, et al. Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. Faseb J. 2001 Aug;15(10):1718–1726.
   PubMed Web of Science ®Google Scholar
• Nagayama T, Hsu S, Zhang M, 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. J Am Coll Cardiol. 2009 Jan 13;53(2):207–215.
   PubMed Web of Science ®Google Scholar
• Ockaili R, Salloum F, Hawkins J, et al. Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial K(ATP) channels in rabbits. Am J Physiol Heart Circ Physiol. 2002 Sep;283(3):H1263–9.
   PubMed Web of Science ®Google Scholar
• Salloum FN, Takenoshita Y, Ockaili RA, et al. Sildenafil and vardenafil but not nitroglycerin limit myocardial infarction through opening of mitochondrial K(ATP) channels when administered at reperfusion following ischemia in rabbits. J Mol Cell Cardiol. 2007 Feb;42(2):453–458.
   PubMed Web of Science ®Google Scholar
• Chau VQ, Salloum FN, Hoke NN, et al. Mitigation of the progression of heart failure with sildenafil involves inhibition of RhoA/Rho-kinase pathway. Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2272–9.
   PubMed Web of Science ®Google Scholar
• Fisher PW, Salloum F, Das A, et al. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation. 2005 Apr 5;111(13):1601–1610.
   PubMed Web of Science ®Google Scholar
• Das A, Xi L, Kukreja RC. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. J Biol Chem. 2005 Apr 1;280(13):12944–12955.
   PubMed Web of Science ®Google Scholar
• Takimoto E, Champion HC, Li M, et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005;11(2):214–222.
   PubMed Web of Science ®Google Scholar
• Hassan MA, Ketat AF. Sildenafil citrate increases myocardial cGMP content in rat heart, decreases its hypertrophic response to isoproterenol and decreases myocardial leak of creatine kinase and troponin T. BMC Pharmacol. 2005 Apr;6(5):10.
   Google Scholar
• Zhang M, Takimoto E, Hsu S, et al. Myocardial remodeling is controlled by myocyte-targeted gene regulation of phosphodiesterase type 5. J Am Coll Cardiol. 2010 Dec 7;56(24):2021–2030.
   PubMed Web of Science ®Google Scholar
• Lukowski R, Rybalkin SD, Loga F, et al. Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes. Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5646–5651.
   PubMed Web of Science ®Google Scholar
• Patrucco E, Domes K, Sbroggio M, et al. Roles of cGMP-dependent protein kinase I (cGKI) and PDE5 in the regulation of Ang II-induced cardiac hypertrophy and fibrosis. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12925–12929.
   PubMed Web of Science ®Google Scholar
• Straubinger J, Schottle V, Bork N, et al. Sildenafil does not prevent heart hypertrophy and fibrosis induced by cardiomyocyte angiotensin ii type 1 receptor signaling. J Pharmacol Exp Ther. 2015 Sep;354(3):406–416.
   PubMed Web of Science ®Google Scholar
• Horvath A, Giatzakis C, Tsang K, et al. A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex. Eur J Hum Genet. 2008 Oct;16(10):1245–1253.
   PubMed Web of Science ®Google Scholar
• Kokkonen-Simon KM, Saberi A, Nakamura T, et al. Marked disparity of microRNA modulation by cGMP-selective PDE5 versus PDE9 inhibitors in heart disease. JCI Insight. 2018 Aug 9;3(15). DOI:https://doi.org/10.1172/jci.insight.121739
   Google Scholar
• Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci. 2016 Oct 13;17(10):1712.
   PubMed Web of Science ®Google Scholar
• Chen S, Yan C. Response by Chen and Yan to Letter Regarding Article, “A Novel Role of Cyclic Nucleotide Phosphodiesterase 10A in Pathological Cardiac Remodeling and Dysfunction”. Circulation. 2020 Jul 21;142(3):e36-e37
   Google Scholar
• Porcu E, Medici M, Pistis G, et al. A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. PLoS Genet. 2013;9(2):e1003266.
   PubMed Web of Science ®Google Scholar
• Hankir MK, Kranz M, Gnad T, et al. A novel thermoregulatory role for PDE10A in mouse and human adipocytes. EMBO Mol Med. 2016 Jul;8(7):796–812.
   PubMed Web of Science ®Google Scholar
• Nawrocki AR, Rodriguez CG, Toolan DM, et al. Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance. Diabetes. 2014 Jan;63(1):300–311.
   PubMed Web of Science ®Google Scholar
• Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation. 2007 Jul 24;116(4):434–448.
   PubMed Web of Science ®Google Scholar
• Ayres JK, Maani CV Milrinone. Treasure Island (FL): StatPearls; 2020.
   Google Scholar
• Young RA, Milrinone WA. A preliminary review of its pharmacological properties and therapeutic use. Drugs. 1988 Aug;36(2):158–192.
   PubMed Web of Science ®Google Scholar
• Chong LYZ, Satya K, Kim B, et al. Milrinone dosing and a culture of caution in clinical practice. Cardiol Rev. 2018 Jan–Feb;26(1):35–42.
   PubMed Web of Science ®Google Scholar
• Dhaliwal A, Gupta M PDE5 inhibitor. Treasure Island (FL): StatPearls; 2020.
   Google Scholar
• Corbin JD, Beasley A, Blount MA, et al. High lung PDE5: a strong basis for treating pulmonary hypertension with PDE5 inhibitors. Biochem Biophys Res Commun. 2005 Sep 2;334(3):930–938.
   PubMed Web of Science ®Google Scholar
• De Vecchis R, Cesaro A, Ariano C, et al. Phosphodiesterase-5 inhibitors improve clinical outcomes, exercise capacity and pulmonary hemodynamics in patients with heart failure with reduced left ventricular ejection fraction: a meta-analysis. J Clin Med Res. 2017 Jun;9(6):488–498.
   PubMedGoogle Scholar
• Guazzi M, Vicenzi M, Arena R, et al. 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. Circ Heart Fail. 2011 Jan;4(1):8–17.
   PubMed Web of Science ®Google Scholar
• Giannetta E, Isidori AM, Galea N, et al. Chronic Inhibition of cGMP phosphodiesterase 5A improves diabetic cardiomyopathy: a randomized, controlled clinical trial using magnetic resonance imaging with myocardial tagging. Circulation. 2012 May 15;125(19):2323–2333.
   PubMed Web of Science ®Google Scholar
• Liu LC, Hummel YM, van der Meer P, et al. Effects of sildenafil on cardiac structure and function, cardiopulmonary exercise testing and health-related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension. Eur J Heart Fail. 2017 Jan;19(1):116–125.
   PubMed Web of Science ®Google Scholar
• Redfield MM, Chen HH, Borlaug BA, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013 Mar 27;309(12):1268–1277.
   PubMed Web of Science ®Google Scholar
• Zhang YS, Li JD, Yan C. An update on vinpocetine: new discoveries and clinical implications. Eur J Pharmacol. 2018 Jan;15(819):30–34.
   Google Scholar
• Snyder PB, Esselstyn JM, Loughney K, et al. The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis. J Lipid Res. 2005 Mar;46(3):494–503.
   PubMed Web of Science ®Google Scholar
• Palmer D, Tsoi K, Maurice DH. Synergistic inhibition of vascular smooth muscle cell migration by phosphodiesterase 3 and phosphodiesterase 4 inhibitors. Circ Res. 1998;82(8):852–861.
   PubMed Web of Science ®Google Scholar
• Kraynik SM, Miyaoka RS, Beavo JA. PDE3 and PDE4 isozyme-selective inhibitors are both required for synergistic activation of brown adipose tissue. Mol Pharmacol. 2013 Jun;83(6):1155–1165.
   PubMed Web of Science ®Google Scholar
• Vinogradova TM, Sirenko S, Lukyanenko YO, et al. Basal spontaneous firing of rabbit sinoatrial node cells is regulated by dual activation of PDEs (phosphodiesterases) 3 and 4. Circ Arrhythm Electrophysiol. 2018 Jun;11(6):e005896.
   PubMed Web of Science ®Google Scholar
• Abbott-Banner KH, Page CP. Dual PDE3/4 and PDE4 inhibitors: novel treatments for COPD and other inflammatory airway diseases. Basic Clin Pharmacol Toxicol. 2014 May;114(5):365–376.
   PubMed Web of Science ®Google Scholar
• Singh D, Martinez FJ, Watz H, et al. A dose-ranging study of the inhaled dual phosphodiesterase 3 and 4 inhibitor ensifentrine in COPD. Respir Res. 2020 Feb 10;21(1):47.
   PubMed Web of Science ®Google Scholar