Abnormal phosphorylation / dephosphorylation and Ca2+ dysfunction in heart failure

1.

Katz AM, Rolett EL (2016) Heart failure: when form fails to follow function. Eur Heart J 37(5):449–454. https://doi.org/10.1093/eurheartj/ehv548CrossRefPubMed

2.

Wu S, Chen L, Zhou X (2022) Circular RNAs in the regulation of cardiac hypertrophy. Mol Ther Nucleic Acids 27:484–490. https://doi.org/10.1016/j.omtn.2021.12.025CrossRefPubMed

3.

Tham YK, Bernardo BC, Ooi JY, Weeks KL, McMullen JR (2015) Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets. Arch Toxicol 89(9):1401–1438. https://doi.org/10.1007/s00204-015-1477-xCrossRefPubMed

4.

Liu Y, Chen J, Fontes SK, Bautista EN, Cheng Z (2022) Physiological and pathological roles of protein kinase A in the heart. Cardiovasc Res 118(2):386–398. https://doi.org/10.1093/cvr/cvab008CrossRefPubMed

5.

Wang J, Gareri C, Rockman HA (2018) G-Protein-coupled receptors in heart disease. Circ Res 123(6):716–735. https://doi.org/10.1161/CIRCRESAHA.118.311403CrossRefPubMedPubMedCentral

6.

Antos CL, Frey N, Marx SO et al (2001) Dilated cardiomyopathy and sudden death resulting from constitutive activation of protein kinase A. Circ Res 89(11):997–1004. https://doi.org/10.1161/hh2301.100003CrossRefPubMed

7.

Bowling N, Walsh RA, Song G et al (1999) Increased protein kinase C activity and expression of Ca²⁺-sensitive isoforms in the failing human heart. Circulation 99(3):384–391. https://doi.org/10.1161/01.cir.99.3.384CrossRefPubMed

8.

Liu Q, Chen X, Macdonnell SM et al (2009) Protein kinase calpha, but not PKCbeta or PKCgamma, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach. Circ Res 105(2):194–200. https://doi.org/10.1161/CIRCRESAHA.109.195313CrossRefPubMedPubMedCentral

9.

Bossuyt J, Helmstadter K, Wu X et al (2008) Ca²⁺/calmodulin-dependent protein kinase IIdelta and protein kinase D overexpression reinforce the histone deacetylase 5 redistribution in heart failure. Circ Res 102(6):695–702. https://doi.org/10.1161/CIRCRESAHA.107.169755CrossRefPubMed

10.

Paulus WJ, Tschope C (2013) A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 62(4):263–271. https://doi.org/10.1016/j.jacc.2013.02.092CrossRefPubMed

11.

Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298(5600):1912–1934. https://doi.org/10.1126/science.1075762ADSCrossRefPubMed

12.

Mattiazzi A, Mundina-Weilenmann C, Guoxiang C, Vittone L, Kranias E (2005) Role of phospholamban phosphorylation on Thr17 in cardiac physiological and pathological conditions. Cardiovasc Res 68(3):366–375. https://doi.org/10.1016/j.cardiores.2005.08.010CrossRefPubMed

13.

Haworth RS, Roberts NA, Cuello F, Avkiran M (2007) Regulation of protein kinase D activity in adult myocardium: novel counter-regulatory roles for protein kinase cepsilon and protein kinase A. J Mol Cell Cardiol 43(6):686–695. https://doi.org/10.1016/j.yjmcc.2007.09.013CrossRefPubMed

14.

Kamel R, Leroy J, Vandecasteele G, Fischmeister R (2023) Cyclic nucleotide phosphodiesterases as therapeutic targets in cardiac hypertrophy and heart failure. Nat Rev Cardiol 20(2):90–108. https://doi.org/10.1038/s41569-022-00756-zCrossRefPubMed

15.

Reyes Gaido OE, Nkashama LJ, Schole KL et al (2023) CaMKII as a therapeutic target in cardiovascular disease. Annu Rev Pharmacol Toxicol 63:249–272. https://doi.org/10.1146/annurev-pharmtox-051421-111814CrossRefPubMed

16.

Steenaart NA, Ganim JR, Di Salvo J, Kranias EG (1992) The phospholamban phosphatase associated with cardiac sarcoplasmic reticulum is a type 1 enzyme. Arch Biochem Biophys 293(1):17–24. https://doi.org/10.1016/0003-9861(92)90359-5CrossRefPubMed

17.

Gupta RC, Mishra S, Rastogi S, Imai M, Habib O, Sabbah HN (2003) Cardiac SR-coupled PP1 activity and expression are increased and inhibitor 1 protein expression is decreased in failing hearts. Am J Physiol Heart Circ Physiol 285(6):H2373–H2381. https://doi.org/10.1152/ajpheart.00442.2003CrossRefPubMed

18.

Yamada M, Ikeda Y, Yano M et al (2006) Inhibition of protein phosphatase 1 by inhibitor-2 gene delivery ameliorates heart failure progression in genetic cardiomyopathy. FASEB J 20(8):1197–1199. https://doi.org/10.1096/fj.05-5299fjeCrossRefPubMed

19.

Lei M, Wang X, Ke Y, Solaro RJ (2015) Regulation of Ca²⁺ transient by PP2A in normal and failing heart. Front Physiol 6:13. https://doi.org/10.3389/fphys.2015.00013CrossRefPubMedPubMedCentral

20.

Beca S, Ahmad F, Shen W et al (2013) Phosphodiesterase type 3A regulates basal myocardial contractility through interacting with sarcoplasmic reticulum calcium ATPase type 2a signaling complexes in mouse heart. Circ Res 112(2):289–297. https://doi.org/10.1161/CIRCRESAHA.111.300003CrossRefPubMed

21.

Beca S, Helli PB, Simpson JA et al (2011) Phosphodiesterase 4D regulates baseline sarcoplasmic reticulum Ca²⁺ release and cardiac contractility, independently of L-type Ca²⁺ current. Circ Res 109(9):1024–1030. https://doi.org/10.1161/CIRCRESAHA.111.250464CrossRefPubMedPubMedCentral

22.

Lehnart SE, Wehrens XH, Reiken S et al (2005) Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell 123(1):25–35. https://doi.org/10.1016/j.cell.2005.07.030CrossRefPubMedPubMedCentral

23.

Lugnier C, Keravis T, Le Bec A, Pauvert O, Proteau S, Rousseau E (1999) Characterization of cyclic nucleotide phosphodiesterase isoforms associated to isolated cardiac nuclei. Biochim Biophys Acta 1472(3):431–446. https://doi.org/10.1016/s0304-4165(99)00145-2CrossRefPubMed

24.

Kranias EG, Solaro RJ (1982) Phosphorylation of troponin I and phospholamban during catecholamine stimulation of rabbit heart. Nature 298(5870):182–184. https://doi.org/10.1038/298182a0ADSCrossRefPubMed

25.

Layland J, Solaro RJ, Shah AM (2005) Regulation of cardiac contractile function by troponin I phosphorylation. Cardiovasc Res 66(1):12–21. https://doi.org/10.1016/j.cardiores.2004.12.022CrossRefPubMed

26.

Pena JR, Wolska BM (2004) Troponin I phosphorylation plays an important role in the relaxant effect of beta-adrenergic stimulation in mouse hearts. Cardiovasc Res 61(4):756–763. https://doi.org/10.1016/j.cardiores.2003.12.019CrossRefPubMed

27.

Salhi HE, Walton SD, Hassel NC et al (2014) Cardiac troponin I tyrosine 26 phosphorylation decreases myofilament Ca²⁺ sensitivity and accelerates deactivation. J Mol Cell Cardiol 76:257–264. https://doi.org/10.1016/j.yjmcc.2014.09.013CrossRefPubMed

28.

Noland TA Jr, Raynor RL, Kuo JF (1989) Identification of sites phosphorylated in bovine cardiac troponin I and troponin T by protein kinase C and comparative substrate activity of synthetic peptides containing the phosphorylation sites. J Biol Chem 264(34):20778–20785CrossRefPubMed

29.

Jideama NM, Noland TA Jr, Raynor RL et al (1996) Phosphorylation specificities of protein kinase C isozymes for bovine cardiac troponin I and troponin T and sites within these proteins and regulation of myofilament properties. J Biol Chem 271(38):23277–23283. https://doi.org/10.1074/jbc.271.38.23277CrossRefPubMed

30.

Swiderek K, Jaquet K, Meyer HE, Schachtele C, Hofmann F, Heilmeyer LM Jr (1990) Sites phosphorylated in bovine cardiac troponin T and I. characterization by 31P-NMR spectroscopy and phosphorylation by protein kinases. Eur J Biochem 190(3):575–582. https://doi.org/10.1111/j.1432-1033.1990.tb15612.xCrossRefPubMed

31.

Papa A, Kushner J, Marx SO (2022) Adrenergic regulation of calcium channels in the heart. Annu Rev Physiol 84:285–306. https://doi.org/10.1146/annurev-physiol-060121-041653CrossRefPubMed

32.

Li L, Cai H, Liu H, Guo T (2015) Beta-adrenergic stimulation activates protein kinase cepsilon and induces extracellular signal-regulated kinase phosphorylation and cardiomyocyte hypertrophy. Mol Med Rep 11(6):4373–4380. https://doi.org/10.3892/mmr.2015.3316CrossRefPubMed

33.

Oestreich EA, Malik S, Goonasekera SA et al (2009) Epac and phospholipase cepsilon regulate Ca²⁺ release in the heart by activation of protein kinase cepsilon and calcium-calmodulin kinase II. J Biol Chem 284(3):1514–1522. https://doi.org/10.1074/jbc.M806994200CrossRefPubMedPubMedCentral

34.

Sjaastad I, Schiander I, Sjetnan A et al (2003) Increased contribution of alpha 1- vs. beta-adrenoceptor-mediated inotropic response in rats with congestive heart failure. Acta Physiol Scand 177(4):449–458. https://doi.org/10.1046/j.1365-201X.2003.01063.xCrossRefPubMed

35.

Suematsu N, Satoh S, Kinugawa S et al (2001) Alpha1-adrenoceptor-Gq-RhoA signaling is upregulated to increase myofibrillar Ca²⁺ sensitivity in failing hearts. Am J Physiol Heart Circ Physiol 281(2):H637–H646. https://doi.org/10.1152/ajpheart.2001.281.2.H637CrossRefPubMed

36.

Hussain RI, Qvigstad E, Birkeland JA et al (2009) Activation of muscarinic receptors elicits inotropic responses in ventricular muscle from rats with heart failure through myosin light chain phosphorylation. Br J Pharmacol 156(4):575–586. https://doi.org/10.1111/j.1750-3639.2009.00016.xCrossRefPubMedPubMedCentral

37.

Yamakage M, Namiki A (2002) Calcium channels–basic aspects of their structure, function and gene encoding: anesthetic action on the channels–a review. Can J Anaesth 49(2):151–164. https://doi.org/10.1007/BF03020488CrossRefPubMed

38.

Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415(6868):198–205. https://doi.org/10.1038/415198aADSCrossRefPubMed

39.

Richard S, Perrier E, Fauconnier J et al (2006) Ca²⁺-induced Ca²⁺ entry’ or how the L-type Ca²⁺ channel remodels its own signalling pathway in cardiac cells. Prog Biophys Mol Biol 90(1–3):118–135. https://doi.org/10.1016/j.pbiomolbio.2005.05.005CrossRefPubMed

40.

Bers DM, Despa S (2006) Cardiac myocytes Ca²⁺ and Na+ regulation in normal and failing hearts. J Pharmacol Sci 100(5):315–322. https://doi.org/10.1254/jphs.cpj06001xCrossRefPubMed

41.

Kamp TJ, Hell JW (2000) Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C. Circ Res 87(12):1095–1102. https://doi.org/10.1161/01.res.87.12.1095CrossRefPubMed

42.

Jurevicius J, Fischmeister R (1996) cAMP compartmentation is responsible for a local activation of cardiac Ca²⁺ channels by beta-adrenergic agonists. Proc Natl Acad Sci USA 93(1):295–299. https://doi.org/10.1073/pnas.93.1.295ADSCrossRefPubMedPubMedCentral

43.

Lindegger N, Niggli E (2005) Paradoxical SR Ca²⁺ release in guinea-pig cardiac myocytes after beta-adrenergic stimulation revealed by two-photon photolysis of caged Ca²⁺. J Physiol 565(Pt 3):801–813. https://doi.org/10.1113/jphysiol.2005.084376CrossRefPubMedPubMedCentral

44.

Mery PF, Abi-Gerges N, Vandecasteele G, Jurevicius J, Eschenhagen T, Fischmeister R (1997) Muscarinic regulation of the L-type calcium current in isolated cardiac myocytes. Life Sci 60(13–14):1113–1120. https://doi.org/10.1016/s0024-3205(97)00055-6CrossRefPubMed

45.

Fischmeister R, Castro LR, Abi-Gerges A et al (2006) Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases. Circ Res 99(8):816–828. https://doi.org/10.1161/01.RES.0000246118.98832.04CrossRefPubMed

46.

Alden KJ, Goldspink PH, Ruch SW, Buttrick PM, Garcia J (2002) Enhancement of L-type Ca²⁺ current from neonatal mouse ventricular myocytes by constitutively active PKC-betaII. Am J Physiol Cell Physiol 282(4):C768–774. https://doi.org/10.1152/ajpcell.00494.2001CrossRefPubMed

47.

Yue Y, Qu Y, Boutjdir M (2004) Beta- and alpha-adrenergic cross-signaling for L-type ca current is impaired in transgenic mice with constitutive activation of epsilon PKC. Biochem Biophys Res Commun 314(3):749–754. https://doi.org/10.1016/j.bbrc.2003.12.155CrossRefPubMed

48.

Gomez AM, Valdivia HH, Cheng H et al (1997) Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science 276(5313):800–806. https://doi.org/10.1126/science.276.5313.800CrossRefPubMed

49.

Ouadid H, Albat B, Nargeot J (1995) Calcium currents in diseased human cardiac cells. J Cardiovasc Pharmacol 25(2):282–291. https://doi.org/10.1097/00005344-199502000-00014CrossRefPubMed

50.

Davare MA, Horne MC, Hell JW (2000) Protein phosphatase 2A is associated with class C L-type calcium channels (Cav1.2) and antagonizes channel phosphorylation by cAMP-dependent protein kinase. J Biol Chem 275(50):39710–39717. https://doi.org/10.1074/jbc.M005462200CrossRefPubMed

51.

Ganesan AN, Maack C, Johns DC, Sidor A, O’Rourke B (2006) Beta-adrenergic stimulation of L-type Ca²⁺ channels in cardiac myocytes requires the distal carboxyl terminus of alpha1C but not serine 1928. Circ Res 98(2):e11–18. https://doi.org/10.1161/01.RES.0000202692.23001.e2CrossRefPubMedPubMedCentral

52.

Yang L, Katchman A, Samad T, Morrow J, Weinberg R, Marx SO (2013) Beta-adrenergic regulation of the L-type Ca²⁺ channel does not require phosphorylation of alpha1C Ser1700. Circ Res 113(7):871–880. https://doi.org/10.1161/CIRCRESAHA.113.301926CrossRefPubMed

53.

Fu Y, Westenbroek RE, Scheuer T, Catterall WA (2014) Basal and beta-adrenergic regulation of the cardiac calcium channel CaV1.2 requires phosphorylation of serine 1700. Proc Natl Acad Sci USA 111(46):16598–16603. https://doi.org/10.1073/pnas.1419129111ADSCrossRefPubMedPubMedCentral

54.

Yang L, Dai DF, Yuan C et al (2016) Loss of beta-adrenergic-stimulated phosphorylation of CaV1.2 channels on Ser1700 leads to heart failure. Proc Natl Acad Sci USA 113(49):E7976–E7985. https://doi.org/10.1073/pnas.1617116113CrossRefPubMedPubMedCentral

55.

Katchman A, Yang L, Zakharov SI et al (2017) Proteolytic cleavage and PKA phosphorylation of alpha(1 C) subunit are not required for adrenergic regulation of ca(V)1.2 in the heart. Proc Natl Acad Sci USA 114(34):9194–9199. https://doi.org/10.1073/pnas.1706054114ADSCrossRefPubMedPubMedCentral

56.

Hulme JT, Lin TW, Westenbroek RE, Scheuer T, Catterall WA (2003) Beta-adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with a kinase-anchoring protein 15. Proc Natl Acad Sci USA 100(22):13093–13098. https://doi.org/10.1073/pnas.2135335100ADSCrossRefPubMedPubMedCentral

57.

Hall DD, Davare MA, Shi M et al (2007) Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons. Biochemistry 46(6):1635–1646. https://doi.org/10.1021/bi062217xCrossRefPubMed

58.

Michalak M, Opas M (2009) Endoplasmic and sarcoplasmic reticulum in the heart. Trends Cell Biol 19(6):253–259. https://doi.org/10.1016/j.tcb.2009.03.006CrossRefPubMed

59.

Marx SO, Reiken S, Hisamatsu Y et al (2000) PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 101(4):365–376. https://doi.org/10.1016/s0092-8674(00)80847-8CrossRefPubMed

60.

Brillantes AB, Ondrias K, Scott A et al (1994) Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein. Cell 77(4):513–523. https://doi.org/10.1016/0092-8674(94)90214-3CrossRefPubMed

61.

Marx SO, Ondrias K, Marks AR (1998) Coupled gating between individual skeletal muscle Ca²⁺ release channels (ryanodine receptors). Science 281(5378):818–821. https://doi.org/10.1126/science.281.5378.818ADSCrossRefPubMed

62.

Kaftan E, Marks AR, Ehrlich BE (1996) Effects of rapamycin on ryanodine receptor/Ca²⁺-release channels from cardiac muscle. Circ Res 78(6):990–997. https://doi.org/10.1161/01.res.78.6.990CrossRefPubMed

63.

Ai X, Curran JW, Shannon TR, Bers DM, Pogwizd SM (2005) Ca²⁺/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca²⁺ leak in heart failure. Circ Res 97(12):1314–1322. https://doi.org/10.1161/01.RES.0000194329.41863.89CrossRefPubMed

64.

Walweel K, Molenaar P, Imtiaz MS et al (2017) Ryanodine receptor modification and regulation by intracellular Ca²⁺ and Mg²⁺ in healthy and failing human hearts. J Mol Cell Cardiol 104:53–62. https://doi.org/10.1016/j.yjmcc.2017.01.016CrossRefPubMed

65.

MacDonnell SM, Garcia-Rivas G, Scherman JA et al (2008) Adrenergic regulation of cardiac contractility does not involve phosphorylation of the cardiac ryanodine receptor at serine 2808. Circ Res 102(8):e65–e72. https://doi.org/10.1161/CIRCRESAHA.108.174722CrossRefPubMedPubMedCentral

66.

Alvarado FJ, Chen X, Valdivia HH (2017) Ablation of the cardiac ryanodine receptor phospho-site Ser2808 does not alter the adrenergic response or the progression to heart failure in mice. Elimination of the genetic background as critical variable. J Mol Cell Cardiol 103:40–47. https://doi.org/10.1016/j.yjmcc.2017.01.001CrossRefPubMedPubMedCentral

67.

Fischer TH, Herting J, Tirilomis T et al (2013) Ca²⁺/calmodulin-dependent protein kinase II and protein kinase A differentially regulate sarcoplasmic reticulum Ca²⁺ leak in human cardiac pathology. Circulation 128(9):970–981. https://doi.org/10.1161/CIRCULATIONAHA.113.001746CrossRefPubMed

68.

Periasamy M, Bhupathy P, Babu GJ (2008) Regulation of sarcoplasmic reticulum Ca²⁺ ATPase pump expression and its relevance to cardiac muscle physiology and pathology. Cardiovasc Res 77(2):265–273. https://doi.org/10.1093/cvr/cvm056CrossRefPubMed

69.

MacLennan DH, Kranias EG (2003) Phospholamban: a crucial regulator of cardiac contractility. Nat Rev Mol Cell Biol 4(7):566–577. https://doi.org/10.1038/nrm1151CrossRefPubMed

70.

Simmerman HK, Jones LR (1998) Phospholamban: protein structure, mechanism of action, and role in cardiac function. Physiol Rev 78(4):921–947. https://doi.org/10.1152/physrev.1998.78.4.921CrossRefPubMed

71.

Brittsan AG, Kranias EG (2000) Phospholamban and cardiac contractile function. J Mol Cell Cardiol 32(12):2131–2139. https://doi.org/10.1006/jmcc.2000.1270CrossRefPubMed

72.

Tada M (1992) Molecular structure and function of phospholamban in regulating the calcium pump from sarcoplasmic reticulum. Ann NY Acad Sci 671:92–102 discussion 102–103. https://doi.org/10.1111/j.1749-6632.1992.tb43787.xADSCrossRefPubMed

73.

Tada M, Inui M (1983) Regulation of calcium transport by the ATPase-phospholamban system. J Mol Cell Cardiol 15(9):565–575. https://doi.org/10.1016/0022-2828(83)90267-5CrossRefPubMed

74.

Tada M, Ohmori F, Kinoshita N, Abe H (1978) Cyclic AMP regulation of active calcium transport across membranes of sarcoplasmic reticulum: role of the 22,000-dalton protein phospholamban. Adv Cycl Nucleotide Res 9:355–369

75.

Kadambi VJ, Kranias EG (1997) Phospholamban: a protein coming of age. Biochem Biophys Res Commun 239(1):1–5. https://doi.org/10.1006/bbrc.1997.7340CrossRefPubMed

76.

Koss KL, Kranias EG (1996) Phospholamban: a prominent regulator of myocardial contractility. Circ Res 79(6):1059–1063. https://doi.org/10.1161/01.res.79.6.1059CrossRefPubMed

77.

Wegener AD, Simmerman HK, Lindemann JP, Jones LR (1989) Phospholamban phosphorylation in intact ventricles. Phosphorylation of serine 16 and threonine 17 in response to beta-adrenergic stimulation. J Biol Chem 264(19):11468–11474CrossRefPubMed

78.

Talosi L, Edes I, Kranias EG (1993) Intracellular mechanisms mediating reversal of beta-adrenergic stimulation in intact beating hearts. Am J Physiol 264(3 Pt 2):H791–H797. https://doi.org/10.1152/ajpheart.1993.264.3.H791CrossRefPubMed

79.

Lindemann JP, Jones LR, Hathaway DR, Henry BG, Watanabe AM (1983) Beta-adrenergic stimulation of phospholamban phosphorylation and Ca²⁺-ATPase activity in guinea pig ventricles. J Biol Chem 258(1):464–471CrossRefPubMed

80.

Garvey JL, Kranias EG, Solaro RJ (1988) Phosphorylation of C-protein, troponin I and phospholamban in isolated rabbit hearts. Biochem J 249(3):709–714. https://doi.org/10.1042/bj2490709CrossRefPubMedPubMedCentral

81.

Mundina-Weilenmann C, Vittone L, Ortale M, de Cingolani GC, Mattiazzi A (1996) Immunodetection of phosphorylation sites gives new insights into the mechanisms underlying phospholamban phosphorylation in the intact heart. J Biol Chem 271(52):33561–33567. https://doi.org/10.1074/jbc.271.52.33561CrossRefPubMed

82.

Sande JB, Sjaastad I, Hoen IB et al (2002) Reduced level of serine(16) phosphorylated phospholamban in the failing rat myocardium: a major contributor to reduced SERCA2 activity. Cardiovasc Res 53(2):382–391. https://doi.org/10.1016/s0008-6363(01)00489-8CrossRefPubMed

83.

Currie S, Smith GL (1999) Enhanced phosphorylation of phospholamban and downregulation of sarco/endoplasmic reticulum Ca²⁺ ATPase type 2 (SERCA 2) in cardiac sarcoplasmic reticulum from rabbits with heart failure. Cardiovasc Res 41(1):135–146. https://doi.org/10.1016/s0008-6363(98)00241-7CrossRefPubMed

84.

Boknik P, Heinroth-Hoffmann I, Kirchhefer U et al (2001) Enhanced protein phosphorylation in hypertensive hypertrophy. Cardiovasc Res 51(4):717–728. https://doi.org/10.1016/s0008-6363(01)00346-7CrossRefPubMed

85.

Mills GD, Kubo H, Harris DM, Berretta RM, Piacentino V 3rd, Houser SR (2006) Phosphorylation of phospholamban at threonine-17 reduces cardiac adrenergic contractile responsiveness in chronic pressure overload-induced hypertrophy. Am J Physiol Heart Circ Physiol 291(1):H61–H70. https://doi.org/10.1152/ajpheart.01353.2005CrossRefPubMed

86.

Schwinger RH, Munch G, Bolck B, Karczewski P, Krause EG, Erdmann E (1999) Reduced Ca²⁺-sensitivity of SERCA 2a in failing human myocardium due to reduced serin-16 phospholamban phosphorylation. J Mol Cell Cardiol 31(3):479–491. https://doi.org/10.1006/jmcc.1998.0897CrossRefPubMed

87.

Aoyama H, Ikeda Y, Miyazaki Y et al (2011) Isoform-specific roles of protein phosphatase 1 catalytic subunits in sarcoplasmic reticulum-mediated Ca²⁺ cycling. Cardiovasc Res 89(1):79–88. https://doi.org/10.1093/cvr/cvq252CrossRefPubMed

88.

van der Velden J, Papp Z, Zaremba R et al (2003) Increased Ca²⁺-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins. Cardiovasc Res 57(1):37–47. https://doi.org/10.1016/s0008-6363(02)00606-5CrossRefPubMed

89.

Pulcastro HC, Awinda PO, Breithaupt JJ, Tanner BC (2016) Effects of myosin light chain phosphorylation on length-dependent myosin kinetics in skinned rat myocardium. Arch Biochem Biophys 601:56–68. https://doi.org/10.1016/j.abb.2015.12.014CrossRefPubMed

90.

Kampourakis T, Sun YB, Irving M (2016) Myosin light chain phosphorylation enhances contraction of heart muscle via structural changes in both thick and thin filaments. Proc Natl Acad Sci USA 113(21):E3039–E3047. https://doi.org/10.1073/pnas.1602776113CrossRefPubMedPubMedCentral

91.

Markandran K, Yu H, Song W, Lam D, Madathummal MC, Ferenczi MA (2021) Functional and molecular characterisation of heart failure progression in mice and the role of myosin regulatory light chains in the recovery of cardiac muscle function. Int J Mol Sci 23(1):88. https://doi.org/10.3390/ijms23010088CrossRefPubMedPubMedCentral

92.

Jacques AM, Copeland O, Messer AE et al (2008) Myosin binding protein C phosphorylation in normal, hypertrophic and failing human heart muscle. J Mol Cell Cardiol 45(2):209–216. https://doi.org/10.1016/j.yjmcc.2008.05.020CrossRefPubMed

93.

Tong CW, Stelzer JE, Greaser ML, Powers PA, Moss RL (2008) Acceleration of crossbridge kinetics by protein kinase a phosphorylation of cardiac myosin binding protein C modulates cardiac function. Circ Res 103(9):974–982. https://doi.org/10.1161/CIRCRESAHA.108.177683CrossRefPubMedPubMedCentral

94.

Gilda JE, Gomes AV (2013) How phosphorylated can it get? Cardiac myosin binding protein C phosphorylation in heart failure. J Mol Cell Cardiol 62:108–110. https://doi.org/10.1016/j.yjmcc.2013.05.015CrossRefPubMed

95.

Gresham KS, Stelzer JE (2016) The contributions of cardiac myosin binding protein C and troponin I phosphorylation to beta-adrenergic enhancement of in vivo cardiac function. J Physiol 594(3):669–686. https://doi.org/10.1113/JP270959CrossRefPubMedPubMedCentral

96.

McNamara JW, Singh RR, Sadayappan S (2019) Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin. Proc Natl Acad Sci USA 116(24):11731–11736. https://doi.org/10.1073/pnas.1821660116ADSCrossRefPubMedPubMedCentral

97.

Messer AE, Jacques AM, Marston SB (2007) Troponin phosphorylation and regulatory function in human heart muscle: dephosphorylation of Ser23/24 on troponin I could account for the contractile defect in end-stage heart failure. J Mol Cell Cardiol 42(1):247–259. https://doi.org/10.1016/j.yjmcc.2006.08.017CrossRefPubMed

98.

Konhilas JP, Irving TC, Wolska BM et al (2003) Troponin I in the murine myocardium: influence on length-dependent activation and interfilament spacing. J Physiol 547(Pt 3):951–961. https://doi.org/10.1113/jphysiol.2002.038117CrossRefPubMedPubMedCentral

99.

Horn K, Leontieva L, Williams JM, Furbee PM, Helmkamp JC, Manley WG 3rd (2002) Alcohol problems among young adult emergency department patients: making predictions using routine sociodemographic information. J Crit Care 17(4):212–220. https://doi.org/10.1053/jcrc.2002.37231CrossRefPubMed

100.

Zhang P, Kirk JA, Ji W et al (2012) Multiple reaction monitoring to identify site-specific troponin I phosphorylated residues in the failing human heart. Circulation 126(15):1828–1837. https://doi.org/10.1161/CIRCULATIONAHA.112.096388CrossRefPubMedPubMedCentral

101.

Wijnker PJ, Sequeira V, Witjas-Paalberends ER et al (2014) Phosphorylation of protein kinase C sites Ser42/44 decreases Ca²⁺-sensitivity and blunts enhanced length-dependent activation in response to protein kinase A in human cardiomyocytes. Arch Biochem Biophys 554:11–21. https://doi.org/10.1016/j.abb.2014.04.017CrossRefPubMedPubMedCentral

102.

Wijnker PJ, Foster DB, Tsao AL et al (2013) Impact of site-specific phosphorylation of protein kinase A sites Ser23 and Ser24 of cardiac troponin I in human cardiomyocytes. Am J Physiol Heart Circ Physiol 304(2):H260–H268. https://doi.org/10.1152/ajpheart.00498.2012CrossRefPubMed

103.

Martin-Garrido A, Biesiadecki BJ, Salhi HE et al (2018) Monophosphorylation of cardiac troponin-I at Ser-23/24 is sufficient to regulate cardiac myofibrillar Ca²⁺ sensitivity and calpain-induced proteolysis. J Biol Chem 293(22):8588–8599. https://doi.org/10.1074/jbc.RA117.001292CrossRefPubMedPubMedCentral

104.

Ravichandran VS, Patel HJ, Pagani FD, Westfall MV (2019) Cardiac contractile dysfunction and protein kinase C-mediated myofilament phosphorylation in disease and aging. J Gen Physiol 151(9):1070–1080. https://doi.org/10.1085/jgp.201912353CrossRefPubMedPubMedCentral

105.

Nixon BR, Walton SD, Zhang B et al (2014) Combined troponin I Ser-150 and Ser-23/24 phosphorylation sustains thin filament Ca²⁺ sensitivity and accelerates deactivation in an acidic environment. J Mol Cell Cardiol 72:177–185. https://doi.org/10.1016/j.yjmcc.2014.03.010CrossRefPubMedPubMedCentral

106.

Salhi HE, Hassel NC, Siddiqui JK et al (2016) Myofilament calcium sensitivity: mechanistic insight into TnI Ser-23/24 and Ser-150 phosphorylation integration. Front Physiol 7:567. https://doi.org/10.3389/fphys.2016.00567CrossRefPubMedPubMedCentral

107.

Kooij V, Zhang P, Piersma SR et al (2013) PKCalpha-specific phosphorylation of the troponin complex in human myocardium: a functional and proteomics analysis. PLoS ONE 8(10):e74847. https://doi.org/10.1371/journal.pone.0074847ADSCrossRefPubMedPubMedCentral

108.

Fugger L, Morling N, Bendtzen K et al (1989) IL-6 gene polymorphism in rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes. J Immunogenet 16(6):461–465. https://doi.org/10.1111/j.1744-313x.1989.tb00495.xCrossRefPubMed

109.

Wijnker PJ, Sequeira V, Foster DB et al (2014) Length-dependent activation is modulated by cardiac troponin I bisphosphorylation at Ser23 and Ser24 but not by Thr143 phosphorylation. Am J Physiol Heart Circ Physiol 306(8):H1171–H1181. https://doi.org/10.1152/ajpheart.00580.2013CrossRefPubMedPubMedCentral

110.

Kooij V, Boontje N, Zaremba R et al (2010) Protein kinase C alpha and epsilon phosphorylation of troponin and myosin binding protein C reduce Ca²⁺ sensitivity in human myocardium. Basic Res Cardiol 105(2):289–300. https://doi.org/10.1007/s00395-009-0053-zCrossRefPubMed

111.

Solaro RJ, Kobayashi T (2011) Protein phosphorylation and signal transduction in cardiac thin filaments. J Biol Chem 286(12):9935–9940. https://doi.org/10.1074/jbc.R110.197731CrossRefPubMedPubMedCentral

112.

Linke WA, Hamdani N (2014) Gigantic business: titin properties and function through thick and thin. Circ Res 114(6):1052–1068. https://doi.org/10.1161/CIRCRESAHA.114.301286CrossRefPubMed

113.

Leite-Moreira AM, Almeida-Coelho J, Neves JS et al (2018) Stretch-induced compliance: a novel adaptive biological mechanism following acute cardiac load. Cardiovasc Res 114(5):656–667. https://doi.org/10.1093/cvr/cvy026CrossRefPubMed

114.

Gomori K, Herwig M, Budde H et al (2022) Ca²⁺/calmodulin-dependent protein kinase II and protein kinase G oxidation contributes to impaired sarcomeric proteins in hypertrophy model. ESC Heart Fail 9(4):2585–2600. https://doi.org/10.1002/ehf2.13973CrossRefPubMedPubMedCentral

115.

Mohamed BA, Schnelle M, Khadjeh S et al (2016) Molecular and structural transition mechanisms in long-term volume overload. Eur J Heart Fail 18(4):362–371. https://doi.org/10.1002/ejhf.465CrossRefPubMed

116.

Hofmann F, Wegener JW (2013) cGMP-dependent protein kinases (cGK). Methods Mol Biol 1020:17–50. https://doi.org/10.1007/978-1-62703-459-3_2CrossRefPubMed

117.

Kovacs A, Herwig M, Budde H et al (2021) Interventricular differences of signaling pathways-mediated regulation of cardiomyocyte function in response to high oxidative stress in the post-ischemic failing rat heart. Antioxid (Basel) 10(6):964. https://doi.org/10.3390/antiox10060964CrossRef

118.

Sugimoto M, Murata M, Yamaoka Y (2020) Chemoprevention of gastric cancer development after Helicobacter pylori eradication therapy in an east Asian population: Meta-analysis. World J Gastroenterol 26(15):1820–1840. https://doi.org/10.3748/wjg.v26.i15.1820CrossRefPubMedPubMedCentral

119.

Carr AN, Schmidt AG, Suzuki Y et al (2002) Type 1 phosphatase, a negative regulator of cardiac function. Mol Cell Biol 22(12):4124–4135. https://doi.org/10.1128/MCB.22.12.4124-4135.2002CrossRefPubMedPubMedCentral

120.

El-Armouche A, Pamminger T, Ditz D, Zolk O, Eschenhagen T (2004) Decreased protein and phosphorylation level of the protein phosphatase inhibitor-1 in failing human hearts. Cardiovasc Res 61(1):87–93. https://doi.org/10.1016/j.cardiores.2003.11.005CrossRefPubMed

121.

Gupta RC, Mishra S, Yang XP, Sabbah HN (2005) Reduced inhibitor 1 and 2 activity is associated with increased protein phosphatase type 1 activity in left ventricular myocardium of one-kidney, one-clip hypertensive rats. Mol Cell Biochem 269(1–2):49–57. https://doi.org/10.1007/s11010-005-2538-xCrossRefPubMed

122.

Huang FL, Glinsmann WH (1976) Separation and characterization of two phosphorylase phosphatase inhibitors from rabbit skeletal muscle. Eur J Biochem 70(2):419–426. https://doi.org/10.1111/j.1432-1033.1976.tb11032.xCrossRefPubMed

123.

Neumann J, Gupta RC, Schmitz W, Scholz H, Nairn AC, Watanabe AM (1991) Evidence for isoproterenol-induced phosphorylation of phosphatase inhibitor-1 in the intact heart. Circ Res 69(6):1450–1457. https://doi.org/10.1161/01.res.69.6.1450CrossRefPubMed

124.

Iyer RB, Koritz SB, Kirchberger MA (1988) A regulation of the level of phosphorylated phospholamban by inhibitor-1 in rat heart preparations in vitro. Mol Cell Endocrinol 55(1):1–6. https://doi.org/10.1016/0303-7207(88)90084-6CrossRefPubMed

125.

Gupta RC, Neumann J, Watanabe AM, Lesch M, Sabbah HN (1996) Evidence for presence and hormonal regulation of protein phosphatase inhibitor-1 in ventricular cardiomyocyte. Am J Physiol 270(Pt 2):H1159–1164. https://doi.org/10.1152/ajpheart.1996.270.4.H1159CrossRefPubMed

126.

El-Armouche A, Bednorz A, Pamminger T et al (2006) Role of calcineurin and protein phosphatase-2A in the regulation of phosphatase inhibitor-1 in cardiac myocytes. Biochem Biophys Res Commun 346(3):700–706. https://doi.org/10.1016/j.bbrc.2006.05.182CrossRefPubMed

127.

Foulkes JG, Strada SJ, Henderson PJ, Cohen P (1983) A kinetic analysis of the effects of inhibitor-1 and inhibitor-2 on the activity of protein phosphatase-1. Eur J Biochem 132(2):309–313. https://doi.org/10.1111/j.1432-1033.1983.tb07363.xCrossRefPubMed

128.

Huang KX, Paudel HK (2000) Ser67-phosphorylated inhibitor 1 is a potent protein phosphatase 1 inhibitor. Proc Natl Acad Sci USA 97(11):5824–5829. https://doi.org/10.1073/pnas.100460897ADSCrossRefPubMedPubMedCentral

129.

Braz JC, Gregory K, Pathak A et al (2004) PKC-alpha regulates cardiac contractility and propensity toward heart failure. Nat Med 10(3):248–254. https://doi.org/10.1038/nm1000CrossRefPubMed

130.

Rodriguez P, Mitton B, Waggoner JR, Kranias EG (2006) Identification of a novel phosphorylation site in protein phosphatase inhibitor-1 as a negative regulator of cardiac function. J Biol Chem 281(50):38599–38608. https://doi.org/10.1074/jbc.M604139200CrossRefPubMed

131.

Park IK, DePaoli-Roach AA (1994) Domains of phosphatase inhibitor-2 involved in the control of the ATP-Mg-dependent protein phosphatase. J Biol Chem 269(46):28919–28928CrossRefPubMed

132.

Yang J, Hurley TD, DePaoli-Roach AA (2000) Interaction of inhibitor-2 with the catalytic subunit of type 1 protein phosphatase. Identification of a sequence analogous to the consensus type 1 protein phosphatase-binding motif. J Biol Chem 275(30):22635–22644. https://doi.org/10.1074/jbc.M003082200CrossRefPubMed

133.

Kirchhefer U, Baba HA, Boknik P et al (2005) Enhanced cardiac function in mice overexpressing protein phosphatase Inhibitor-2. Cardiovasc Res 68(1):98–108. https://doi.org/10.1016/j.cardiores.2005.05.019CrossRefPubMed

134.

Wehrens XH, Lehnart SE, Reiken SR et al (2004) Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2. Science 304(5668):292–296. https://doi.org/10.1126/science.1094301ADSCrossRefPubMed

135.

Yano M, Ono K, Ohkusa T et al (2000) Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca²⁺ leak through ryanodine receptor in heart failure. Circulation 102(17):2131–2136. https://doi.org/10.1161/01.cir.102.17.2131CrossRefPubMed

136.

Redfield MM, Chen HH, Borlaug BA et al (2013) Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 309(12):1268–1277. https://doi.org/10.1001/jama.2013.2024CrossRefPubMed

137.

Miller CL, Oikawa M, Cai Y et al (2009) Role of Ca²⁺/calmodulin-stimulated cyclic nucleotide phosphodiesterase 1 in mediating cardiomyocyte hypertrophy. Circ Res 105(10):956–964. https://doi.org/10.1161/CIRCRESAHA.109.198515CrossRefPubMedPubMedCentral

138.

Miller CL, Cai Y, Oikawa M et al (2011) Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart. Basic Res Cardiol 106(6):1023–1039. https://doi.org/10.1007/s00395-011-0228-2CrossRefPubMedPubMedCentral

139.

Wu MP, Zhang YS, Xu X, Zhou Q, Li JD, Yan C (2017) Vinpocetine attenuates pathological cardiac remodeling by inhibiting Cardiac Hypertrophy and Fibrosis. Cardiovasc Drugs Ther 31(2):157–166. https://doi.org/10.1007/s10557-017-6719-0CrossRefPubMedPubMedCentral

140.

Hashimoto T, Kim GE, Tunin RS et al (2018) Acute enhancement of cardiac function by phosphodiesterase type 1 inhibition. Circulation 138(18):1974–1987. https://doi.org/10.1161/CIRCULATIONAHA.117.030490CrossRefPubMedPubMedCentral

141.

Gilotra NA, DeVore AD, Povsic TJ et al (2021) Acute hemodynamic effects and tolerability of phosphodiesterase-1 inhibition with ITI-214 in human systolic heart failure. Circ Heart Fail 14(9):e008236. https://doi.org/10.1161/CIRCHEARTFAILURE.120.008236CrossRefPubMedPubMedCentral

142.

Aye TT, Soni S, van Veen TA et al (2012) Reorganized PKA-AKAP associations in the failing human heart. J Mol Cell Cardiol 52(2):511–518. https://doi.org/10.1016/j.yjmcc.2011.06.003CrossRefPubMed

143.

Mehel H, Emons J, Vettel C et al (2013) Phosphodiesterase-2 is up-regulated in human failing hearts and blunts beta-adrenergic responses in cardiomyocytes. J Am Coll Cardiol 62(17):1596–1606. https://doi.org/10.1016/j.jacc.2013.05.057CrossRefPubMed

144.

Galindo-Tovar A, Vargas ML, Kaumann AJ (2018) Phosphodiesterase PDE2 activity, increased by isoprenaline, does not reduce beta-adrenoceptor-mediated chronotropic and inotropic effects in rat heart. Naunyn Schmiedebergs Arch Pharmacol 391(6):571–585. https://doi.org/10.1007/s00210-018-1480-xCrossRefPubMed

145.

Zoccarato A, Surdo NC, Aronsen JM et al (2015) Cardiac hypertrophy is inhibited by a local pool of cAMP regulated by phosphodiesterase 2. Circ Res 117(8):707–719. https://doi.org/10.1161/CIRCRESAHA.114.305892CrossRefPubMed

146.

Baliga RS, Preedy MEJ, Dukinfield MS et al (2018) Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure. Proc Natl Acad Sci USA 115(31):E7428–E7437. https://doi.org/10.1073/pnas.1800996115CrossRefPubMedPubMedCentral

147.

Vettel C, Lindner M, Dewenter M et al (2017) Phosphodiesterase 2 protects against catecholamine-induced arrhythmia and preserves contractile function after myocardial infarction. Circ Res 120(1):120–132. https://doi.org/10.1161/CIRCRESAHA.116.310069CrossRefPubMed

148.

Wagner M, Sadek MS, Dybkova N et al (2021) Cellular mechanisms of the anti-arrhythmic effect of Cardiac PDE2 overexpression. Int J Mol Sci 22(9):4816. https://doi.org/10.3390/ijms22094816CrossRefPubMedPubMedCentral

149.

Liu K, Li D, Hao G et al (2018) Phosphodiesterase 2A as a therapeutic target to restore cardiac neurotransmission during sympathetic hyperactivity. JCI Insight 3(9):e98694. https://doi.org/10.1172/jci.insight.98694CrossRefPubMedPubMedCentral

150.

Barbagallo F, Xu B, Reddy GR et al (2016) Genetically encoded biosensors reveal PKA hyperphosphorylation on the myofilaments in rabbit heart failure. Circ Res 119(8):931–943. https://doi.org/10.1161/CIRCRESAHA.116.308964CrossRefPubMedPubMedCentral

151.

Verde I, Pahlke G, Salanova M et al (2001) Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase. J Biol Chem 276(14):11189–11198. https://doi.org/10.1074/jbc.M006546200CrossRefPubMed

152.

Dodge-Kafka KL, Soughayer J, Pare GC et al (2005) The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways. Nature 437(7058):574–578. https://doi.org/10.1038/nature03966ADSCrossRefPubMedPubMedCentral

153.

Dodge KL, Khouangsathiene S, Kapiloff MS et al (2001) mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO J 20(8):1921–1930. https://doi.org/10.1093/emboj/20.8.1921CrossRefPubMedPubMedCentral

154.

Ahmad F, Shen W, Vandeput F et al (2015) 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 290(11):6763–6776. https://doi.org/10.1074/jbc.M115.638585CrossRefPubMedPubMedCentral

155.

Vandecasteele G, Verde I, Rucker-Martin C, Donzeau-Gouge P, Fischmeister R (2001) Cyclic GMP regulation of the L-type Ca²⁺ channel current in human atrial myocytes. J Physiol 533(Pt 2):329–340. https://doi.org/10.1111/j.1469-7793.2001.0329a.xCrossRefPubMedPubMedCentral

156.

Leroy J, Abi-Gerges A, Nikolaev VO et al (2008) Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca²⁺ channel regulation in adult rat ventricular myocytes: role of phosphodiesterases. Circ Res 102(9):1091–1100. https://doi.org/10.1161/CIRCRESAHA.107.167817CrossRefPubMed

157.

Verde I, Vandecasteele G, Lezoualc’h F, Fischmeister R (1999) Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca²⁺ current in rat ventricular myocytes. Br J Pharmacol 127(1):65–74. https://doi.org/10.1038/sj.bjp.0702506CrossRefPubMedPubMedCentral

158.

Ono K, Trautwein W (1991) Potentiation by cyclic GMP of beta-adrenergic effect on Ca²⁺ current in guinea-pig ventricular cells. J Physiol 443:387–404. https://doi.org/10.1113/jphysiol.1991.sp018839CrossRefPubMedPubMedCentral

159.

Fischmeister R, Hartzell HC (1990) Regulation of calcium current by low-Km cyclic AMP phosphodiesterases in cardiac cells. Mol Pharmacol 38(3):426–433PubMed

160.

Yano M, Kohno M, Ohkusa T et al (2000) Effect of milrinone on left ventricular relaxation and Ca²⁺ uptake function of cardiac sarcoplasmic reticulum. Am J Physiol Heart Circ Physiol 279(4):H1898–H1905. https://doi.org/10.1152/ajpheart.2000.279.4.H1898CrossRefPubMed

161.

Malecot CO, Bers DM, Katzung BG (1986) Biphasic contractions induced by milrinone at low temperature in ferret ventricular muscle: role of the sarcoplasmic reticulum and transmembrane calcium influx. Circ Res 59(2):151–162. https://doi.org/10.1161/01.res.59.2.151CrossRefPubMed

162.

Movsesian MA, Smith CJ, Krall J, Bristow MR, Manganiello VC (1991) Sarcoplasmic reticulum-associated cyclic adenosine 5’-monophosphate phosphodiesterase activity in normal and failing human hearts. J Clin Invest 88(1):15–19. https://doi.org/10.1172/JCI115272CrossRefPubMedPubMedCentral

163.

von der Leyen H, Mende U, Meyer W et al (1991) Mechanism underlying the reduced positive inotropic effects of the phosphodiesterase III inhibitors pimobendan, adibendan and saterinone in failing as compared to nonfailing human cardiac muscle preparations. Naunyn Schmiedebergs Arch Pharmacol 344(1):90–100. https://doi.org/10.1007/BF00167387CrossRefPubMed

164.

Ding B, Abe JI, Wei H et al (2005) Functional role of phosphodiesterase 3 in cardiomyocyte apoptosis: implication in heart failure. Circulation 111(19):2469–2476. https://doi.org/10.1161/01.CIR.0000165128.39715.87CrossRefPubMedPubMedCentral

165.

Mika D, Bobin P, Lindner M et al (2019) Synergic PDE3 and PDE4 control intracellular cAMP and cardiac excitation-contraction coupling in a porcine model. J Mol Cell Cardiol 133:57–66. https://doi.org/10.1016/j.yjmcc.2019.05.025CrossRefPubMed

166.

Abi-Gerges A, Richter W, Lefebvre F et al (2009) Decreased expression and activity of cAMP phosphodiesterases in cardiac hypertrophy and its impact on beta-adrenergic cAMP signals. Circ Res 105(8):784–792. https://doi.org/10.1161/CIRCRESAHA.109.197947CrossRefPubMedPubMedCentral

167.

Ding B, Abe J, Wei H et al (2005) A positive feedback loop of phosphodiesterase 3 (PDE3) and inducible cAMP early repressor (ICER) leads to cardiomyocyte apoptosis. Proc Natl Acad Sci USA 102(41):14771–14776. https://doi.org/10.1073/pnas.0506489102ADSCrossRefPubMedPubMedCentral

168.

Smith CJ, He J, Ricketts SG, Ding JZ, Moggio RA, Hintze TH (1998) Downregulation of right ventricular phosphodiesterase PDE-3A mRNA and protein before the development of canine heart failure. Cell Biochem Biophys 29(1–2):67–88. https://doi.org/10.1007/BF02737829CrossRefPubMed

169.

Smith CJ, Huang R, Sun D et al (1997) Development of decompensated dilated cardiomyopathy is associated with decreased gene expression and activity of the milrinone-sensitive cAMP phosphodiesterase PDE3A. Circulation 96(9):3116–3123. https://doi.org/10.1161/01.cir.96.9.3116CrossRefPubMed

170.

Hanna R, Nour-Eldine W, Saliba Y et al (2021) Cardiac phosphodiesterases are differentially increased in diabetic cardiomyopathy. Life Sci 283:119857. https://doi.org/10.1016/j.lfs.2021.119857CrossRefPubMed

171.

Polidovitch N, Yang S, Sun H et al (2019) Phosphodiesterase type 3A (PDE3A), but not type 3B (PDE3B), contributes to the adverse cardiac remodeling induced by pressure overload. J Mol Cell Cardiol 132:60–70. https://doi.org/10.1016/j.yjmcc.2019.04.028CrossRefPubMed

172.

Li EA, Xi W, Han YS, Brozovich FV (2019) Phosphodiesterase expression in the normal and failing heart. Arch Biochem Biophys 662:160–168. https://doi.org/10.1016/j.abb.2018.12.013CrossRefPubMed

173.

Takahashi K, Osanai T, Nakano T, Wakui M, Okumura K (2002) Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure. Heart Vessels 16(6):249–256. https://doi.org/10.1007/s003800200032CrossRefPubMed

174.

Holmes JR, Kubo SH, Cody RJ, Kligfield P (1985) Milrinone in congestive heart failure: observations on ambulatory ventricular arrhythmias. Am Heart J 110(4):800–806. https://doi.org/10.1016/0002-8703(85)90460-0CrossRefPubMed

175.

DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R (1989) A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med 320(11):677–683. https://doi.org/10.1056/NEJM198903163201101CrossRefPubMed

176.

Beard MB, Olsen AE, Jones RE, Erdogan S, Houslay MD, Bolger GB (2000) UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions. J Biol Chem 275(14):10349–10358. https://doi.org/10.1074/jbc.275.14.10349CrossRefPubMed

177.

Hoffmann R, Baillie GS, MacKenzie SJ, Yarwood SJ, Houslay MD (1999) The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. EMBO J 18(4):893–903. https://doi.org/10.1093/emboj/18.4.893CrossRefPubMedPubMedCentral

178.

Mika D, Bobin P, Pomerance M et al (2013) Differential regulation of cardiac excitation-contraction coupling by cAMP phosphodiesterase subtypes. Cardiovasc Res 100(2):336–346. https://doi.org/10.1093/cvr/cvt193CrossRefPubMedPubMedCentral

179.

Abi-Gerges A, Castro L, Leroy J, Domergue V, Fischmeister R, Vandecasteele G (2021) Selective changes in cytosolic beta-adrenergic cAMP signals and L-type calcium channel regulation by phosphodiesterases during cardiac hypertrophy. J Mol Cell Cardiol 150:109–121. https://doi.org/10.1016/j.yjmcc.2020.10.011CrossRefPubMed

180.

Qvigstad E, Moltzau LR, Aronsen JM et al (2010) Natriuretic peptides increase beta1-adrenoceptor signalling in failing hearts through phosphodiesterase 3 inhibition. Cardiovasc Res 85(4):763–772. https://doi.org/10.1093/cvr/cvp364CrossRefPubMed

181.

Minamisawa S, Hoshijima M, Chu G et al (1999) Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 99(3):313–322. https://doi.org/10.1016/s0092-8674(00)81662-1CrossRefPubMed

182.

Schwinger RH, Bohm M, Schmidt U et al (1995) Unchanged protein levels of SERCA II and phospholamban but reduced Ca²⁺ uptake and Ca²⁺-ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation 92(11):3220–3228. https://doi.org/10.1161/01.cir.92.11.3220CrossRefPubMed

183.

Meyer M, Schillinger W, Pieske B et al (1995) Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy. Circulation 92(4):778–784. https://doi.org/10.1161/01.cir.92.4.778CrossRefPubMed

184.

Takimoto E, Champion HC, Belardi D et al (2005) cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circ Res 96(1):100–109. https://doi.org/10.1161/01.RES.0000152262.22968.72CrossRefPubMed

185.

Mokni W, Keravis T, Etienne-Selloum N et al (2010) Concerted regulation of cGMP and cAMP phosphodiesterases in early cardiac hypertrophy induced by angiotensin II. PLoS ONE 5(12):e14227. https://doi.org/10.1371/journal.pone.0014227ADSCrossRefPubMedPubMedCentral

186.

Pokreisz P, Vandenwijngaert S, Bito V et al (2009) Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice. Circulation 119(3):408–416. https://doi.org/10.1161/CIRCULATIONAHA.108.822072CrossRefPubMedPubMedCentral

187.

Nagendran J, Archer SL, Soliman D et al (2007) Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation 116(3):238–248. https://doi.org/10.1161/CIRCULATIONAHA.106.655266CrossRefPubMed

188.

Shan X, Quaile MP, Monk JK, French B, Cappola TP, Margulies KB (2012) Differential expression of PDE5 in failing and nonfailing human myocardium. Circ Heart Fail 5(1):79–86. https://doi.org/10.1161/CIRCHEARTFAILURE.111.961706CrossRefPubMed

189.

Garcia AM, Nakano SJ, Karimpour-Fard A et al (2018) Phosphodiesterase-5 is elevated in failing single ventricle myocardium and affects cardiomyocyte remodeling in vitro. Circ Heart Fail 11(9):e004571. https://doi.org/10.1161/CIRCHEARTFAILURE.117.004571CrossRefPubMedPubMedCentral

190.

Senzaki H, Smith CJ, Juang GJ et al (2001) Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J 15(10):1718–1726. https://doi.org/10.1096/fj.00-0538comCrossRefPubMed

191.

Takimoto E, Champion HC, Li M et al (2005) Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11(2):214–222. https://doi.org/10.1038/nm1175CrossRefPubMed

192.

Nakata TM, Suzuki K, Uemura A, Shimada K, Tanaka R (2019) Contrasting effects of Inhibition of phosphodiesterase 3 and 5 on cardiac function and interstitial fibrosis in rats with isoproterenol-induced cardiac dysfunction. J Cardiovasc Pharmacol 73(3):195–205. https://doi.org/10.1097/FJC.0000000000000652CrossRefPubMed

193.

Guazzi M, Vicenzi M, Arena R, Guazzi MD (2011) 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 4(1):8–17. https://doi.org/10.1161/CIRCHEARTFAILURE.110.944694CrossRefPubMed

194.

Soderling SH, Bayuga SJ, Beavo JA (1998) Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase. Proc Natl Acad Sci USA 95(15):8991–8996. https://doi.org/10.1073/pnas.95.15.8991ADSCrossRefPubMedPubMedCentral

195.

Wang H, Yan Z, Yang S, Cai J, Robinson H, Ke H (2008) Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity. Biochemistry 47(48):12760–12768. https://doi.org/10.1021/bi801487xCrossRefPubMed

196.

Patrucco E, Albergine MS, Santana LF, Beavo JA (2010) Phosphodiesterase 8A (PDE8A) regulates excitation-contraction coupling in ventricular myocytes. J Mol Cell Cardiol 49(2):330–333. https://doi.org/10.1016/j.yjmcc.2010.03.016CrossRefPubMedPubMedCentral

197.

Methawasin M, Strom J, Borkowski T et al (2020) Phosphodiesterase 9a Inhibition in mouse models of diastolic dysfunction. Circ Heart Fail 13(5):e006609. https://doi.org/10.1161/CIRCHEARTFAILURE.119.006609CrossRefPubMedPubMedCentral

198.

Scott NJA, Rademaker MT, Charles CJ, Espiner EA, Richards AM (2019) Hemodynamic, hormonal, and renal actions of phosphodiesterase-9 inhibition in experimental heart failure. J Am Coll Cardiol 74(7):889–901. https://doi.org/10.1016/j.jacc.2019.05.067CrossRefPubMed

199.

Chen S, Zhang Y, Lighthouse JK et al (2020) A novel role of cyclic nucleotide phosphodiesterase 10A in pathological cardiac remodeling and dysfunction. Circulation 141(3):217–233. https://doi.org/10.1161/CIRCULATIONAHA.119.042178CrossRefPubMed

200.

Hall DD, Feekes JA, Arachchige Don AS et al (2006) Binding of protein phosphatase 2A to the L-type calcium channel Cav1.2 next to Ser1928, its main PKA site, is critical for Ser1928 dephosphorylation. Biochemistry 45(10):3448–3459. https://doi.org/10.1021/bi051593zCrossRefPubMed

201.

El Refaey M, Musa H, Murphy NP et al (2019) Protein phosphatase 2A regulates cardiac Na(+) channels. Circ Res 124(5):737–746. https://doi.org/10.1161/CIRCRESAHA.118.314350CrossRefPubMedPubMedCentral

202.

Lubelwana Hafver T, Wanichawan P, Manfra O et al (2017) Mapping the in vitro interactome of cardiac sodium Na+-calcium Ca²⁺ exchanger 1 (NCX1). Proteomics 17:17–18. https://doi.org/10.1002/pmic.201600417CrossRef

203.

Hua F, Wu Z, Yan X et al (2018) DR region of Na(+)-K(+)-ATPase is a new target to protect heart against oxidative injury. Sci Rep 8(1):13100. https://doi.org/10.1038/s41598-018-31460-zADSCrossRefPubMedPubMedCentral

204.

Belevych AE, Sansom SE, Terentyeva R et al (2011) MicroRNA-1 and – 133 increase arrhythmogenesis in heart failure by dissociating phosphatase activity from RyR2 complex. PLoS ONE 6(12):e28324. https://doi.org/10.1371/journal.pone.0028324ADSCrossRefPubMedPubMedCentral

205.

Terentyev D, Belevych AE, Terentyeva R et al (2009) miR-1 overexpression enhances Ca²⁺ release and promotes cardiac arrhythmogenesis by targeting PP2A regulatory subunit B56alpha and causing CaMKII-dependent hyperphosphorylation of RyR2. Circ Res 104(4):514–521. https://doi.org/10.1161/CIRCRESAHA.108.181651CrossRefPubMedPubMedCentral

206.

Jideama NM, Crawford BH, Hussain AK, Raynor RL (2006) Dephosphorylation specificities of protein phosphatase for cardiac troponin I, troponin T, and sites within troponin T. Int J Biol Sci 2(1):1–9. https://doi.org/10.7150/ijbs.2.1CrossRefPubMedPubMedCentral

207.

Yin X, Cuello F, Mayr U et al (2010) Proteomics analysis of the cardiac myofilament subproteome reveals dynamic alterations in phosphatase subunit distribution. Mol Cell Proteom 9(3):497–509. https://doi.org/10.1074/mcp.M900275-MCP200CrossRef

208.

Mumby MC, Russell KL, Garrard LJ, Green DD (1987) Cardiac contractile protein phosphatases. Purification of two enzyme forms and their characterization with subunit-specific antibodies. J Biol Chem 262(13):6257–6265CrossRefPubMed

209.

Wu SC, Solaro RJ (2007) Protein kinase C zeta. A novel regulator of both phosphorylation and de-phosphorylation of cardiac sarcomeric proteins. J Biol Chem 282(42):30691–30698. https://doi.org/10.1074/jbc.M703670200CrossRefPubMed

210.

Surks HK, Mochizuki N, Kasai Y et al (1999) Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha. Science 286(5444):1583–1587. https://doi.org/10.1126/science.286.5444.1583CrossRefPubMed

211.

Ravan H, Yazdanparast R (2012) Development of a new loop-mediated isothermal amplification assay for prt (rfbS) gene to improve the identification of salmonella serogroup D. World J Microbiol Biotechnol 28(5):2101–2106. https://doi.org/10.1007/s11274-012-1014-5CrossRefPubMed

212.

Cai Z, Wu C, Xu Y, Cai J, Zhao M, Zu L (2023) The NO-cGMP-PKG Axis in HFpEF: from pathological mechanisms to potential therapies. Aging Dis 14(1):46–62. https://doi.org/10.14336/AD.2022.0523CrossRefPubMedPubMedCentral

213.

Ladage D, Tilemann L, Ishikawa K et al (2011) Inhibition of PKCalpha/beta with ruboxistaurin antagonizes heart failure in pigs after myocardial infarction injury. Circ Res 109(12):1396–1400. https://doi.org/10.1161/CIRCRESAHA.111.255687CrossRefPubMedPubMedCentral

214.

Zhang J, Liang R, Wang K et al (2022) Novel CaMKII-delta inhibitor hesperadin exerts dual functions to ameliorate cardiac ischemia/reperfusion injury and inhibit tumor growth. Circulation 145(15):1154–1168. https://doi.org/10.1161/CIRCULATIONAHA.121.055920CrossRefPubMed

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abnormal phosphorylation / dephosphorylation and Ca²⁺ dysfunction in heart failure

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page