Top

Published in:

01-11-2019 | Heart Failure

Advances in research on treatment of heart failure with nitrosyl hydrogen

Authors: Yanqing Guo, Jiyao Xu, Li Wu, Yongzhi Deng, Jingping Wang, Jian An

Published in: Heart Failure Reviews | Issue 6/2019

Abstract

Heart failure is the end stage of various heart diseases such as ischemic heart disease, dilated cardiomyopathy, valvular heart disease, congenital heart disease, and hypertensive myocardial damage. It is characterized by a decrease in myocardial contractility, but there is currently no ideal treatment. Nitroxyl hydrogen (HNO) is considered to be a protonated form of NO. It has special chemical properties compared to other nitrogen oxides. In the body of organisms, HNO can participate in all aspects of the occurrence and development of heart failure (HF) and react with some proteins closely related to cardiac activity, changing its spatial structure and exerting cardioprotective effects. In recent years, studies have shown that HNO can inhibit cardiomyocyte hypertrophy, reduce inflammation, enhance myocardial contractility, dilate coronary arteries as well as peripheral blood vessels in early heart failure, and protect the heart against heart failure. This paper, combined with the latest research results at home and abroad, clarifies that nitrosyl hydrogen exerts cardioprotective effects through various processes that occur in the development of heart failure.

Fukuto JM, Cisneros CJ, Kinkade RL (2013) A comparison of the chemistry associated with the biological signaling and actions of nitroxyl (HNO) and nitric oxide (NO). J Inorg Biochem 118:201–208. https://doi.org/10.1016/j.jinorgbio.2012.08.027 CrossRefPubMed

Sabbah HN, Tocchetti CG, Wang M, Daya S, Gupta RC, Tunin RS, Mazhari R, Takimoto E, Paolocci N, Cowart D, Colucci WS, Kass DA (2013) Nitroxyl (HNO): a novel approach for the acute treatment of heart failure. Circ Heart Fail 6:1250–1258. https://doi.org/10.1161/circheartfailure.113.000632 CrossRefPubMedPubMedCentral

Tocchetti CG, Wang W, Froehlich JP, Huke S, Aon MA, Wilson GM, di Benedetto G, O’Rourke B, Gao WD, Wink DA, Toscano JP, Zaccolo M, Bers DM, Valdivia HH, Cheng H, Kass DA, Paolocci N (2007) Nitroxyl improves cellular heart function by directly enhancing cardiac sarcoplasmic reticulum Ca2+ cycling. Circ Res 100:96–104. https://doi.org/10.1161/01.RES.0000253904.53601.c9 CrossRefPubMed

Chin KY, Michel L, Qin CX, Cao N, Woodman OL, Ritchie RH (2016) The HNO donor Angeli's salt offers potential haemodynamic advantages over NO or dobutamine in ischaemia-reperfusion injury in the rat heart ex vivo. Pharmacol Res 104:165–175. https://doi.org/10.1016/j.phrs.2015.12.006 CrossRefPubMed

Zhu G, Groneberg D, Sikka G, Hori D, Ranek MJ, Nakamura T, Takimoto E, Paolocci N, Berkowitz DE, Friebe A, Kass DA (2015) Soluble guanylate cyclase is required for systemic vasodilation but not positive inotropy induced by nitroxyl in the mouse. Hypertension 65:385–392. https://doi.org/10.1161/hypertensionaha.114.04285 CrossRefPubMed

Dautov RF, Ngo DT, Licari G, Liu S, Sverdlov AL, Ritchie RH et al (2013) The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness. Nitric Oxide 35:72–78. https://doi.org/10.1016/j.niox.2013.08.006 CrossRefPubMed

Tocchetti CG, Carpi A, Coppola C, Quintavalle C, Rea D, Campesan M, Arcari A, Piscopo G, Cipresso C, Monti MG, de Lorenzo C, Arra C, Condorelli G, di Lisa F, Maurea N (2014) Ranolazine protects from doxorubicin-induced oxidative stress and cardiac dysfunction. Eur J Heart Fail 16:358–366. https://doi.org/10.1002/ejhf.50 CrossRefPubMed

Bers DM (2006) Altered cardiac myocyte ca regulation in heart failure. Physiology (Bethesda) 21:380–387. https://doi.org/10.1152/physiol.00019.2006 CrossRef

Curran J, Hinton MJ, Rios E, Bers DM, Shannon TR (2007) Beta-adrenergic enhancement of sarcoplasmic reticulum calcium leak in cardiac myocytes is mediated by calcium/calmodulin-dependent protein kinase. Circ Res 100:391–398. https://doi.org/10.1161/01.RES.0000258172.74570.e6 CrossRefPubMed

10.

Santulli G, Xie W, Reiken SR, Marks AR (2015) Mitochondrial calcium overload is a key determinant in heart failure. Proc Natl Acad Sci U S A 112:11389–11394. https://doi.org/10.1073/pnas.1513047112 CrossRefPubMedPubMedCentral

11.

Vafiadaki E, Papalouka V, Arvanitis DA, Kranias EG, Sanoudou D (2009) The role of SERCA2a/PLN complex, ca(2+) homeostasis, and anti-apoptotic proteins in determining cell fate. Pflugers Arch 457:687–700. https://doi.org/10.1007/s00424-008-0506-5 CrossRefPubMed

12.

Hasenfuss G, Teerlink JR (2011) Cardiac inotropes: current agents and future directions. Eur Heart J 32:1838–1845. https://doi.org/10.1093/eurheartj/ehr026 CrossRefPubMed

13.

Tarone G, Balligand JL, Bauersachs J, Clerk A, De Windt L, Heymans S et al (2014) Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the working group on myocardial function of the European Society of Cardiology. Eur J Heart Fail 16:494–508. https://doi.org/10.1002/ejhf.62 CrossRefPubMed

14.

Nagy L, Pollesello P, Papp Z (2014) Inotropes and inodilators for acute heart failure: sarcomere active drugs in focus. J Cardiovasc Pharmacol 64:199–208. https://doi.org/10.1097/fjc.0000000000000113 CrossRefPubMedPubMedCentral

15.

Nediani C, Raimondi L, Borchi E, Cerbai E (2011) Nitric oxide/reactive oxygen species generation and nitroso/redox imbalance in heart failure: from molecular mechanisms to therapeutic implications. Antioxid Redox Signal 14:289–331. https://doi.org/10.1089/ars.2010.3198 CrossRefPubMed

16.

Irvine JC, Cao N, Gossain S, Alexander AE, Love JE, Qin C, Horowitz JD, Kemp-Harper BK, Ritchie RH (2013) HNO/cGMP-dependent antihypertrophic actions of isopropylamine-NONOate in neonatal rat cardiomyocytes: potential therapeutic advantages of HNO over NO. Am J Physiol Heart Circ Physiol 305:H365–H377. https://doi.org/10.1152/ajpheart.00495.2012 CrossRefPubMed

17.

Cao N, Wong YG, Rosli S, Kiriazis H, Huynh K, Qin C, du XJ, Kemp-Harper BK, Ritchie RH (2015) Chronic administration of the nitroxyl donor 1-nitrosocyclo hexyl acetate limits left ventricular diastolic dysfunction in a mouse model of diabetes mellitus in vivo. Circ Heart Fail 8:572–581. https://doi.org/10.1161/circheartfailure.114.001699 CrossRefPubMed

18.

Zgheib C, Kurdi M, Zouein FA, Gunter BW, Stanley BA, Zgheib J, Romero DG, King SB, Paolocci N, Booz GW (2012) Acyloxy nitroso compounds inhibit LIF signaling in endothelial cells and cardiac myocytes: evidence that STAT3 signaling is redox-sensitive. PLoS One 7:e43313. https://doi.org/10.1371/journal.pone.0043313 CrossRefPubMedPubMedCentral

19.

Lin EQ, Irvine JC, Cao AH, Alexander AE, Love JE, Patel R, McMullen JR, Kaye DM, Kemp-Harper BK, Ritchie RH (2012) Nitroxyl (HNO) stimulates soluble guanylyl cyclase to suppress cardiomyocyte hypertrophy and superoxide generation. PLoS One 7:e34892. https://doi.org/10.1371/journal.pone.0034892 CrossRefPubMedPubMedCentral

20.

Chin KY, Qin C, Cao N, Kemp-Harper BK, Woodman OL, Ritchie RH (2014) The concomitant coronary vasodilator and positive inotropic actions of the nitroxyl donor Angeli's salt in the intact rat heart: contribution of soluble guanylyl cyclase-dependent and -independent mechanisms. Br J Pharmacol 171:1722–1734. https://doi.org/10.1111/bph.12568 CrossRefPubMedPubMedCentral

21.

Fukuto JM, Jackson MI, Kaludercic N, Paolocci N (2008) Examining nitroxyl in biological systems. Methods Enzymol 440:411–431. https://doi.org/10.1016/s0076-6879(07)00826-9 CrossRefPubMed

22.

Alexander SP, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M et al (2013) The concise guide to PHARMACOLOGY 2013/14: enzymes. Br J Pharmacol 170:1797–1867. https://doi.org/10.1111/bph.12451 CrossRefPubMedPubMedCentral

23.

Keceli G, Moore CD, Labonte JW, Toscano JP (2013) NMR detection and study of hydrolysis of HNO-derived sulfinamides. Biochemistry 52:7387–7396. https://doi.org/10.1021/bi401110f CrossRefPubMed

24.

Kumar MR, Fukuto JM, Miranda KM, Farmer PJ (2010) Reactions of HNO with heme proteins: new routes to HNO-heme complexes and insight into physiological effects. Inorg Chem 49:6283–6292. https://doi.org/10.1021/ic902319d CrossRefPubMedPubMedCentral

25.

Nagahara N (2011) Intermolecular disulfide bond to modulate protein function as a redox-sensing switch. Amino Acids 41:59–72. https://doi.org/10.1007/s00726-010-0508-4 CrossRefPubMed

26.

Fukuto JM, Carrington SJ (2011) HNO signaling mechanisms. Antioxid Redox Signal 14:1649–1657. https://doi.org/10.1089/ars.2010.3855 CrossRefPubMed

27.

Tocchetti CG, Stanley BA, Murray CI, Sivakumaran V, Donzelli S, Mancardi D, Pagliaro P, Gao WD, van Eyk J, Kass DA, Wink DA, Paolocci N (2011) Playing with cardiac “redox switches”: the “HNO way” to modulate cardiac function. Antioxid Redox Signal 14:1687–1698. https://doi.org/10.1089/ars.2010.3859 CrossRefPubMedPubMedCentral

28.

Meissner G (2010) Regulation of ryanodine receptor ion channels through posttranslational modifications. Curr Top Membr 66:91–113. https://doi.org/10.1016/s1063-5823(10)66005-x CrossRefPubMedPubMedCentral

29.

Ge Y, Moss RL (2012) Nitroxyl, redox switches, cardiac myofilaments, and heart failure: a prequel to novel therapeutics? Circ Res 111:954–956. https://doi.org/10.1161/circresaha.112.278416 CrossRefPubMedPubMedCentral

30.

Sivakumaran V, Stanley BA, Tocchetti CG, Ballin JD, Caceres V, Zhou L, Keceli G, Rainer PP, Lee DI, Huke S, Ziolo MT, Kranias EG, Toscano JP, Wilson GM, O'Rourke B, Kass DA, Mahaney JE, Paolocci N (2013) HNO enhances SERCA2a activity and cardiomyocyte function by promoting redox-dependent phospholamban oligomerization. Antioxid Redox Signal 19:1185–1197. https://doi.org/10.1089/ars.2012.5057 CrossRefPubMedPubMedCentral

31.

Lopez BE, Rodriguez CE, Pribadi M, Cook NM, Shinyashiki M, Fukuto JM (2005) Inhibition of yeast glycolysis by nitroxyl (HNO): mechanism of HNO toxicity and implications to HNO biology. Arch Biochem Biophys 442:140–148. https://doi.org/10.1016/j.abb.2005.07.012 CrossRefPubMed

32.

Cheong E, Tumbev V, Abramson J, Salama G, Stoyanovsky DA (2005) Nitroxyl triggers Ca2+ release from skeletal and cardiac sarcoplasmic reticulum by oxidizing ryanodine receptors. Cell Calcium 37:87–96. https://doi.org/10.1016/j.ceca.2004.07.001 CrossRefPubMed

33.

Adak S, Wang Q, Stuehr DJ (2000) Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric-oxide synthase. Implications for mechanism. J Biol Chem 275:33554–33561. https://doi.org/10.1074/jbc.M004337200 CrossRef

34.

DuMond JF, King SB (2011) The chemistry of nitroxyl-releasing compounds. Antioxid Redox Signal 14:1637–1648. https://doi.org/10.1089/ars.2010.3838 CrossRefPubMedPubMedCentral

35.

Miranda KM, Dutton AS, Ridnour LA, Foreman CA, Ford E, Paolocci N, Katori T, Tocchetti CG, Mancardi D, Thomas DD, Espey MG, Houk KN, Fukuto JM, Wink DA (2005) Mechanism of aerobic decomposition of Angeli’s salt (sodium trioxodinitrate) at physiological pH. J Am Chem Soc 127:722–731. https://doi.org/10.1021/ja045480z CrossRefPubMed

36.

Miranda KM, Katori T, Torres de Holding CL, Thomas L, Ridnour LA, McLendon WJ et al (2005) Comparison of the NO and HNO donating properties of diazeniumdiolates: primary amine adducts release HNO in vivo. J Med Chem 48:8220–8228. https://doi.org/10.1021/jm050151i CrossRefPubMed

37.

Gao WD, Murray CI, Tian Y, Zhong X, DuMond JF, Shen X et al (2012) Nitroxyl-mediated disulfide bond formation between cardiac myofilament cysteines enhances contractile function. Circ Res 111:1002–1011. https://doi.org/10.1161/circresaha.112.270827 CrossRefPubMedPubMedCentral

38.

Ritchie RH, Rosenkranz AC, Huynh LP, Stephenson T, Kaye DM, Dusting GJ (2004) Activation of IP prostanoid receptors prevents cardiomyocyte hypertrophy via cAMP-dependent signaling. Am J Physiol Heart Circ Physiol 287:H1179–H1185. https://doi.org/10.1152/ajpheart.00725.2003 CrossRefPubMed

39.

Selvetella G, Hirsch E, Notte A, Tarone G, Lembo G (2004) Adaptive and maladaptive hypertrophic pathways: points of convergence and divergence. Cardiovasc Res 63:373–380. https://doi.org/10.1016/j.cardiores.2004.04.031 CrossRefPubMed

40.

Ritchie RH, Irvine JC, Rosenkranz AC, Patel R, Wendt IR, Horowitz JD, Kemp-Harper BK (2009) Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy: NO* and beyond. Pharmacol Ther 124:279–300. https://doi.org/10.1016/j.pharmthera.2009.08.001 CrossRefPubMed

41.

Bernardo BC, Weeks KL, Pretorius L, McMullen JR (2010) Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies. Pharmacol Ther 128:191–227. https://doi.org/10.1016/j.pharmthera.2010.04.005 CrossRefPubMed

42.

Xu Q, Dalic A, Fang L, Kiriazis H, Ritchie RH, Sim K, Gao XM, Drummond G, Sarwar M, Zhang YY, Dart AM, du XJ (2011) Myocardial oxidative stress contributes to transgenic beta(2)-adrenoceptor activation-induced cardiomyopathy and heart failure. Br J Pharmacol 162:1012–1028. https://doi.org/10.1111/j.1476-5381.2010.01043.x CrossRefPubMedPubMedCentral

43.

Purcell NH, Wilkins BJ, York A, Saba-El-Leil MK, Meloche S, Robbins J et al (2007) Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo. Proc Natl Acad Sci U S A 104:14074–14079. https://doi.org/10.1073/pnas.0610906104 CrossRefPubMedPubMedCentral

44.

Bermejo E, Saenz DA, Alberto F, Rosenstein RE, Bari SE, Lazzari MA (2005) Effect of nitroxyl on human platelets function. Thromb Haemost 94:578–584. https://doi.org/10.1160/th05-01-0062 CrossRefPubMed

45.

Taflin C, Favier B, Baudhuin J, Savenay A, Hemon P, Bensussan A, Charron D, Glotz D, Mooney N (2011) Human endothelial cells generate Th17 and regulatory T cells under inflammatory conditions. Proc Natl Acad Sci U S A 108:2891–2896. https://doi.org/10.1073/pnas.1011811108 CrossRefPubMedPubMedCentral

46.

Hertelendi Z, Toth A, Borbely A, Galajda Z, van der Velden J, Stienen GJ et al (2008) Oxidation of myofilament protein sulfhydryl groups reduces the contractile force and its Ca2+ sensitivity in human cardiomyocytes. Antioxid Redox Signal 10:1175–1184. https://doi.org/10.1089/ars.2007.2014 CrossRefPubMed

47.

Lancel S, Zhang J, Evangelista A, Trucillo MP, Tong X, Siwik DA, Cohen RA, Colucci WS (2009) Nitroxyl activates SERCA in cardiac myocytes via glutathiolation of cysteine 674. Circ Res 104:720–723. https://doi.org/10.1161/circresaha.108.188441 CrossRefPubMedPubMedCentral

48.

Cuffe MS, Califf RM, Adams KF Jr, Benza R, Bourge R, Colucci WS et al (2002) Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. Jama 287:1541–1547CrossRef

49.

Froehlich JP, Mahaney JE, Keceli G, Pavlos CM, Goldstein R, Redwood AJ, Sumbilla C, Lee DI, Tocchetti CG, Kass DA, Paolocci N, Toscano JP (2008) Phospholamban thiols play a central role in activation of the cardiac muscle sarcoplasmic reticulum calcium pump by nitroxyl. Biochemistry 47:13150–13152. https://doi.org/10.1021/bi801925p CrossRefPubMed

50.

Dai T, Tian Y, Tocchetti CG, Katori T, Murphy AM, Kass DA, Paolocci N, Gao WD (2007) Nitroxyl increases force development in rat cardiac muscle. J Physiol 580:951–960. https://doi.org/10.1113/jphysiol.2007.129254 CrossRefPubMedPubMedCentral

51.

Katori T, Hoover DB, Ardell JL, Helm RH, Belardi DF, Tocchetti CG, Forfia PR, Kass DA, Paolocci N (2005) Calcitonin gene-related peptide in vivo positive inotropy is attributable to regional sympatho-stimulation and is blunted in congestive heart failure. Circ Res 96:234–243. https://doi.org/10.1161/01.RES.0000152969.42117.ca CrossRefPubMed

52.

Andrews KL, Lumsden NG, Farry J, Jefferis AM, Kemp-Harper BK, Chin-Dusting JP (2015) Nitroxyl: a vasodilator of human vessels that is not susceptible to tolerance. Clin Sci (Lond) 129:179–187. https://doi.org/10.1042/cs20140759 CrossRef

53.

Irvine JC, Ritchie RH, Favaloro JL, Andrews KL, Widdop RE, Kemp-Harper BK (2008) Nitroxyl (HNO): the Cinderella of the nitric oxide story. Trends Pharmacol Sci 29:601–608. https://doi.org/10.1016/j.tips.2008.08.005 CrossRefPubMed

54.

Zeller A, Wenzl MV, Beretta M, Stessel H, Russwurm M, Koesling D, Schmidt K, Mayer B (2009) Mechanisms underlying activation of soluble guanylate cyclase by the nitroxyl donor Angeli’s salt. Mol Pharmacol 76:1115–1122. https://doi.org/10.1124/mol.109.059915 CrossRefPubMed

55.

Favaloro JL, Kemp-Harper BK (2009) Redox variants of NO (NO {middle dot} and HNO) elicit vasorelaxation of resistance arteries via distinct mechanisms. Am J Physiol Heart Circ Physiol 296:H1274–H1280. https://doi.org/10.1152/ajpheart.00008.2009 CrossRefPubMed

56.

Favaloro JL, Kemp-Harper BK (2007) The nitroxyl anion (HNO) is a potent dilator of rat coronary vasculature. Cardiovasc Res 73:587–596. https://doi.org/10.1016/j.cardiores.2006.11.018 CrossRefPubMed

Title: Advances in research on treatment of heart failure with nitrosyl hydrogen
Authors: Yanqing Guo
Jiyao Xu
Li Wu
Yongzhi Deng
Jingping Wang
Jian An
Publication date: 01-11-2019
Publisher: Springer US
Keyword: Heart Failure
Published in: Heart Failure Reviews / Issue 6/2019
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-019-09800-6

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The STEP trials

Springer Medicine

Advances in research on treatment of heart failure with nitrosyl hydrogen

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

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2019

Cardio-oncology, the myth of Sisyphus, and cardiovascular disease in breast cancer survivors

A review of fibroblast growth factor 21 in diabetic cardiomyopathy

Sudden death in heart failure with preserved ejection fraction and beyond: an elusive target

Advances in targeted therapy for chronic thromboembolic pulmonary hypertension

Research progress on the pathogenesis of CTEPH

Immune cell diversity contributes to the pathogenesis of myocarditis

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