Saxagliptin and tadalafil differentially alter cyclic guanosine monophosphate (cGMP) signaling and left ventricular function in aortic-banded mini-swine

Journal of the American Heart Association

Volumn 5, Issue 4, 2016, Pages

  Hiemstra, Jessica A ^a   Lee, Dong I ^d   Chakir, Khalid ^d   Gutiérrez Aguilar, Manuel ^c   Marshall, Kurt D ^a,c   Zgoda, Pamela J ^a   Rivera, Noelany Cruz ^a   Dozier, Daniel G ^a   Ferguson, Brian S ^a   Heublein, Denise M ^e   Burnett, John C ^e   Scherf, Carolin ^a   Ivey, Jan R ^a   Minervini, Gianmaria ^a,f   McDonald, Kerry S ^b   Baines, Christopher P ^a,b,c   Krenz, Maike ^b,c   Domeier, Timothy L ^b   Emter, Craig A ^a  

^a UNIVERSITY OF MISSOURI   (United States)

^b University of Missouri   (United States)

^c UNIVERSITY OF MISSOURI   (United States)

^d DEPARTMENT OF PATHOLOGY   (United States)

^e MAYO CLINIC   (United States)

^f ASTRAZENECA   (United Kingdom)

Author keywords

cGMP PKG PDE5; Heart failure with preserved ejection fraction; Pressure overload; Saxagliptin; Tadalafil

Indexed keywords

BRAIN NATRIURETIC PEPTIDE; CYCLIC GMP; CYCLIC GMP DEPENDENT PROTEIN KINASE; DIPEPTIDYL PEPTIDASE IV; NEUROPEPTIDE Y; PHOSPHODIESTERASE V; SAXAGLIPTIN; TADALAFIL; ADAMANTANE; ATRIAL NATRIURETIC FACTOR; DIPEPTIDE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; PHOSPHODIESTERASE V INHIBITOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARDIAC MUSCLE CELL; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR PARAMETERS; CELL STRUCTURE; CONTROLLED STUDY; DRUG BLOOD LEVEL; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART LEFT VENTRICLE CONTRACTILITY; HEART LEFT VENTRICLE FUNCTION; HEART LEFT VENTRICLE HYPERTROPHY; HEART PROTECTION; HEART VENTRICLE REMODELING; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; MINIPIG; MITOCHONDRIAL RESPIRATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; SIGNAL TRANSDUCTION; TWO DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY; ANALOGS AND DERIVATIVES; ANIMAL; BLOOD; DIAGNOSTIC IMAGING; DISEASE MODEL; DRUG EFFECTS; ECHOCARDIOGRAPHY; HYPERTROPHY, LEFT VENTRICULAR; MALE; PHYSIOLOGY; PIG;

ADAMANTANE; ANIMALS; ATRIAL NATRIURETIC FACTOR; CYCLIC GMP; DIPEPTIDES; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DISEASE MODELS, ANIMAL; ECHOCARDIOGRAPHY; HYPERTROPHY, LEFT VENTRICULAR; MALE; NATRIURETIC PEPTIDE, BRAIN; NEUROPEPTIDE Y; PHOSPHODIESTERASE 5 INHIBITORS; SIGNAL TRANSDUCTION; SWINE; SWINE, MINIATURE; TADALAFIL; VENTRICULAR FUNCTION, LEFT;

EID: 84995554939     PISSN: None     EISSN: 20479980     Source Type: Journal    
DOI: 10.1161/JAHA.116.003277     Document Type: Article

References (52)

1. Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011;32:670-679.
2. Maeder MT, Kaye DM. Heart failure with normal left ventricular ejection fraction. J Am Coll Cardiol. 2009;53:905-918.
3. Oktay AA, Rich JD, Shah SJ. The emerging epidemic of heart failure with preserved ejection fraction. Curr Heart Fail Rep. 2013;10:401-410.
4. Sharma K, Kass DA. Heart failure with preserved ejection fraction: mechanisms, clinical features, and therapies. Circ Res. 2014;115:79-96.
5. Greene SJ, Gheorghiade M, Borlaug BA, Pieske B, Vaduganathan M, Burnett JC Jr, Roessig L, Stasch JP, Solomon SD, Paulus WJ, Butler J. The cGMP signaling pathway as a therapeutic target in heart failure with preserved ejection fraction. J Am Heart Assoc. 2013;2:e000536.
6. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005;11:214-222.
7. Borbely A, Falcao-Pires I, van Heerebeek L, Hamdani N, Edes I, Gavina C, Leite-Moreira AF, Bronzwaer JG, Papp Z, van der Velden J, Stienen GJ, Paulus WJ. Hypophosphorylation of the stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium. Circ Res. 2009;104:780-786.
8. Kruger M, Kotter S, Grutzner A, Lang P, Andresen C, Redfield MM, Butt E, dos Remedios CG, Linke WA. Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs. Circ Res. 2009;104:87-94.
9. van Heerebeek L, Hamdani N, Falcao-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW, Niessen HW, Paulus WJ. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation. 2012;126:830-839.
10. Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther. 2009;122:216-238.
11. dos Santos L, Salles TA, Arruda-Junior DF, Campos LC, Pereira AC, Barreto AL, Antonio EL, Mansur AJ, Tucci PJ, Krieger JE, Girardi AC. Circulating dipeptidyl peptidase IV activity correlates with cardiac dysfunction in human and experimental heart failure. Circ Heart Fail. 2013;6:1029-1038.
12. Brandt I, Lambeir AM, Ketelslegers JM, Vanderheyden M, Scharpe S, De Meester I. Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form. Clin Chem. 2006;52:82-87.
13. Boerrigter G, Costello-Boerrigter LC, Harty GJ, Lapp H, Burnett JC Jr. Desserine-proline brain natriuretic peptide 3-32 in cardiorenal regulation. Am J Physiol Regul Integr Comp Physiol. 2007;292:R897-R901.
14. Scheen AJ. Cardiovascular effects of gliptins. Nat Rev Cardiol. 2013;10:73-84.
15. Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, Shi V, Bransford T, Takeuchi M, Gong J, Lefkowitz M, Packer M,McMurray JJ; Prospective comparison of AwARBoMOhfwpefI. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012;380:1387-1395.
16. Hiemstra JA, Gutierrez-Aguilar M, Marshall KD, McCommis KS, Zgoda PJ, Cruz-Rivera N, Jenkins NT, Krenz M, Domeier TL, Baines CP, Emter CA. A new twist on an old idea part 2: cyclosporine preserves normal mitochondrial but not cardiomyocyte function in mini-swine with compensated heart failure. Physiol Rep. 2014;2:e12050.
17. Hiemstra JA, Liu S, Ahlman MA, Schuleri KH, Lardo AC, Baines CP, Dellsperger KC, Bluemke DA, Emter CA. A new twist on an old idea: a twodimensional speckle tracking assessment of cyclosporine as a therapeutic alternative for heart failure with preserved ejection fraction. Physiol Rep. 2013;1:e00174.
18. Marshall KD, Muller BN, Krenz M, Hanft LM, McDonald KS, Dellsperger KC, Emter CA. Heart failure with preserved ejection fraction: chronic low-intensity interval exercise training preserves myocardial O2 balance and diastolic function. J Appl Physiol. 2013;114:131-147.
19. Emter CA, Baines CP. Low-intensity aerobic interval training attenuates pathological left ventricular remodeling and mitochondrial dysfunction in aortic-banded miniature swine. Am J Physiol Heart Circ Physiol. 2010;299: H1348-H1356.
20. Wrishko R, Sorsaburu S, Wong D, Strawbridge A, McGill J. Safety, efficacy, and pharmacokinetic overview of low-dose daily administration of tadalafil. J Sex Med. 2009;6:2039-2048.
21. Mondillo S, Galderisi M, Mele D, Cameli M, Lomoriello VS, Zaca V, Ballo P, D'Andrea A, Muraru D, Losi M, Agricola E, D'Errico A, Buralli S, Sciomer S, Nistri S, Badano L; Echocardiography Study Group Of The Italian Society Of C. Speckle-tracking echocardiography: a new technique for assessing myocardial function. J Ultrasound Med. 2011;30:71-83.
22. Russel IK, Gotte MJ, Bronzwaer JG, Knaapen P, Paulus WJ, van Rossum AC. Left ventricular torsion: an expanding role in the analysis of myocardial dysfunction. JACC Cardiovasc Imaging. 2009;2:648-655.
23. McDonald KS, Hanft LM, Domeier TL, Emter CA. Length and PKA dependence of force generation and loaded shortening in porcine cardiac myocytes. Biochem Res Int. 2012;2012:371415.
24. Lee DI, Zhu G, Sasaki T, Cho GS, Hamdani N, Holewinski R, Jo SH, Danner T, Zhang M, Rainer PP, Bedja D, Kirk JA, Ranek MJ, Dostmann WR, Kwon C, Margulies KB, Van Eyk JE, Paulus WJ, Takimoto E, Kass DA. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature. 2015;519:472-476.
25. Burnett JC Jr, Kao PC, Hu DC, Heser DW, Heublein D, Granger JP, Opgenorth TJ, Reeder GS. Atrial natriuretic peptide elevation in congestive heart failure in the human. Science. 1986;231:1145-1147.
26. Seilhamer JJ, Arfsten A, Miller JA, Lundquist P, Scarborough RM, Lewicki JA, Porter JG. Human and canine gene homologs of porcine brain natriuretic peptide. Biochem Biophys Res Commun. 1989;165:650-658.
27. Sudoh T, Maekawa K, Kojima M, Minamino N, Kangawa K, Matsuo H. Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide. Biochem Biophys Res Commun. 1989;159:1427-1434.
28. Pieske B, Kretschmann B, Meyer M, Holubarsch C, Weirich J, Posival H, Minami K, Just H, Hasenfuss G. Alterations in intracellular calcium handling associated with the inverse force-frequency relation in human dilated cardiomyopathy. Circulation. 1995;92:1169-1178.
29. Sabatini S, Sgro P, Duranti G, Ceci R, Di Luigi L. Tadalafil alters energy metabolism in C2C12 skeletal muscle cells. Acta Biochim Pol. 2011;58:237-241.
30. Ishikawa K, Aguero J, Oh JG, Hammoudi N, Fish LA, Leonardson L, Picatoste B, Santos-Gallego CG, Fish KM, Hajjar RJ. Increased stiffness is the major early abnormality in a pig model of severe aortic stenosis and predisposes to congestive heart failure in the absence of systolic dysfunction. J Am Heart Assoc. 2015;4:e001925.
31. Yarbrough WM, Mukherjee R, Stroud RE, Rivers WT, Oelsen JM, Dixon JA, Eckhouse SR, Ikonomidis JS, Zile MR, Spinale FG. Progressive induction of left ventricular pressure overload in a large animal model elicits myocardial remodeling and a unique matrix signature. J Thorac Cardiovasc Surg. 2012;143:215-223.
32. Ye Y, Gong G, Ochiai K, Liu J, Zhang J. High-energy phosphate metabolism and creatine kinase in failing hearts: a new porcine model. Circulation. 2001;103:1570-1576.
33. Szardien S, Mollmann H, Voss S, Troidl C, Rolf A, Liebetrau C, Rixe J, Elsasser A, Hamm CW, Nef HM. Elevated serum levels of neuropeptide Y in stress cardiomyopathy. Int J Cardiol. 2011;147:155-157.
34. Dvorakova MC, Kruzliak P, Rabkin SW. Role of neuropeptides in cardiomyopathies. Peptides. 2014;61:1-6.
35. Shanks J, Herring N. Peripheral cardiac sympathetic hyperactivity in cardiovascular disease: role of neuropeptides. Am J Physiol Regul Integr Comp Physiol. 2013;305:R1411-R1420.
36. Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Parlongo S, Cutrupi S, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Cataliotti A, Malatino LS. Neuropeptide Y, left ventricular mass and function in patients with end stage renal disease. J Hypertens. 2003;21:1355-1362.
37. Santos-Gallego CG, Vahl TP, Goliasch G, Picatoste B, Arias T, Ishikawa K, Njerve IU, Sanz J, Narula J, Sengupta P, Hajjar RJ, Fuster V, Badimon JJ. The sphingosine 1-phosphate receptor agonist fingolimod increases myocardial salvage and decreases adverse post-infarction left ventricular remodeling in a porcine model of ischemia-reperfusion. Circulation. 2016;133:954-966.
38. Zhang R, Niu H, Kang X, Ban T, Hong H, Ai J. Long-term administration of neuropeptide Y in the subcutaneous infusion results in cardiac dysfunction and hypertrophy in rats. Cell Physiol Biochem. 2015;37:94-104.
39. Anamthathmakula P, Sahu M, Sahu A. Evidence suggesting phosphodiesterase-3B regulation of NPY/AgRP gene expression in mHypoE-46 hypothalamic neurons. Neurosci Lett. 2015;604:113-118.
40. Morris DA, Boldt LH, Eichstadt H, Ozcelik C, Haverkamp W. Myocardial systolic and diastolic performance derived by 2-dimensional speckle tracking echocardiography in heart failure with normal left ventricular ejection fraction. Circ Heart Fail. 2012;5:610-620.
41. Carlsson M, Ugander M, Heiberg E, Arheden H. The quantitative relationship between longitudinal and radial function in left, right, and total heart pumping in humans. Am J Physiol Heart Circ Physiol. 2007;293:H636-H644.
42. Pavlopoulos H, Nihoyannopoulos P. Abnormal segmental relaxation patterns in hypertensive disease and symptomatic diastolic dysfunction detected by strain echocardiography. J Am Soc Echocardiogr. 2008;21:899-906.
43. Schiattarella GG, Hill JA. Inhibition of hypertrophy is a good therapeutic strategy in ventricular pressure overload. Circulation. 2015;131:1435-1447.
44. Hoffmann LS, Chen HH. cGMP: transition from bench to bedside: a report of the 6th international conference on cGMP generators, effectors and therapeutic implications. Naunyn Schmiedebergs Arch Pharmacol. 2014;387:707-718.
45. Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011;124:164-174.
46. Moens AL, Takimoto E, Tocchetti CG, Chakir K, Bedja D, Cormaci G, Ketner EA, Majmudar M, Gabrielson K, Halushka MK, Mitchell JB, Biswal S, Channon KM, Wolin MS, Alp NJ, Paolocci N, Champion HC, Kass DA. Reversal of cardiac hypertrophy and fibrosis from pressure overload by tetrahydrobiopterin: efficacy of recoupling nitric oxide synthase as a therapeutic strategy. Circulation. 2008;117:2626-2636.
47. Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O'Connor CM, Felker GM, Goldsmith SR, Bart BA, McNulty SE, Ibarra JC, Lin G, Oh JK, Patel MR, Kim RJ, Tracy RP, Velazquez EJ, Anstrom KJ, Hernandez AF, Mascette AM, Braunwald E; Trial R. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309:1268-1277.
48. Aburaya M, Minamino N, Kangawa K, Tanaka K, Matsuo H. Distribution and molecular forms of brain natriuretic peptide in porcine heart and blood. Biochem Biophys Res Commun. 1989;165:872-879.
49. Lee DI, Kass DA. Phosphodiesterases and cyclic GMP regulation in heart muscle. Physiology (Bethesda). 2012;27:248-258.
50. Zhang M, Kass DA. Phosphodiesterases and cardiac cGMP: evolving roles and controversies. Trends Pharmacol Sci. 2011;32:360-365.
51. Pokreisz P, Vandenwijngaert S, Bito V, Van den Bergh A, Lenaerts I, Busch C, Marsboom G, Gheysens O, Vermeersch P, Biesmans L, Liu X, Gillijns H, Pellens M, Van Lommel A, Buys E, Schoonjans L, Vanhaecke J, Verbeken E, Sipido K, Herijgers P, Bloch KD, Janssens SP. 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;119:408-416.
52. Nagendran J, Archer SL, Soliman D, Gurtu V, Moudgil R, Haromy A, St Aubin C, Webster L, Rebeyka IM, Ross DB, Light PE, Dyck JR, Michelakis ED. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007;116:238-248.