The Thyroid-Oxidative Stress Axis in Heart Failure

  • Melania Gaggini
  • Irene Traghella
  • Cristina VassalleEmail author


Increased or reduced action of thyroid hormones (THs), both hyper- and hypothyroidism, may have relevant cardiovascular effects, which include regulation of cardiac contractility and heart rate, diastolic function, and systemic vascular resistance, thus affecting the onset and development of heart failure (HF). Many of these actions are determined by thyroid-induced oxidative stress modulation, for example, through the direct production of hydrogen peroxide (H2O2) during the synthesis of THs. Oxidative stress alteration, as both increased oxidative stress and reduced availability of antioxidants, exacerbated oxidation of low density lipoproteins, modulated nitric oxide bioavailability, and increased inflammation. These events have been clearly involved in any phase of HF development and extent. The present review aims to discuss oxidative stress status under altered thyroid states in HF pathology.


Thyroid hormones Oxidative stress Heart failure Biomarkers 



A sincere thanks to Dr. Laura SABATINO for proofreading this manuscript.


  1. 1.
    Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem. 2006;52:601–23.PubMedCrossRefGoogle Scholar
  2. 2.
    Ho E, Karimi Galougahi K, Liu CC, Bhindi R, Figtree GA. Biological markers of oxidative stress: applications to cardiovascular research and practice. Redox Biol. 2013;1:483–91.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Resch U, Helsel G, Tatzber F, Sinzinger H. Antioxidant status in thyroid dysfunction. Clin Chem Lab Med. 2002;40:1132–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Mancini A, Di Segni C, Raimondo S, Olivieri G, Silvestrini A, Meucci E, Currò D. Thyroid hormones, oxidative stress, and inflammation. Mediat Inflamm. 2016;2016:6757154.CrossRefGoogle Scholar
  5. 5.
    Elnakish MT, Ahmed AA, Mohler PJ, Janssen PM. Role of oxidative stress in thyroid hormone-induced cardiomyocyte hypertrophy and associated cardiac dysfunction: an undisclosed story. Oxidative Med Cell Longev. 2015;2015:854265.CrossRefGoogle Scholar
  6. 6.
    Costa VM, Carvalho F, Duarte JA, Bastos Mde L, Remião F. The heart as a target for xenobiotic toxicity: the cardiac susceptibility to oxidative stress. Chem Res Toxicol. 2013;26:1285–311.PubMedCrossRefGoogle Scholar
  7. 7.
    Ayoub KF, Pothineni NVK, Rutland J, Ding Z, Mehta JL. Immunity, inflammation, and oxidative stress in heart failure: emerging molecular targets. Cardiovasc Drugs Ther. 2017;31:593–608.PubMedCrossRefGoogle Scholar
  8. 8.
    Ortiga-Carvalho TM, Sidhaye AR, Wondisford FE. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nat Rev Endocrinol. 2014;10:582–91.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Mishra P, Samanta L. Oxidative stress and heart failure in altered thyroid states. ScientificWorldJournal. 2012;2012:741861.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Gredilla R, Barja G, López-Torres M. Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA in the mouse heart. Free Radic Res. 2001;35:417–25.PubMedCrossRefGoogle Scholar
  11. 11.
    Venditti P, Di Meo S. Thyroid hormone-induced oxidative stress. Cell Mol Life Sci. 2006;63:414–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Venditti P, Balestrieri M, Di Meo S, De Leo T. Effect of thyroid state on lipid peroxidation, antioxidant defences, and susceptibility to oxidative stress in rat tissues. J Endocrinol. 1997;155:151–7.PubMedCrossRefGoogle Scholar
  13. 13.
    da Rosa Araujo AS, Silva de Miranda MF, de Oliveira UO, Fernandes T, Llesuy S, Rios Kucharski LC, Khaper N, Belló-Klein A. Increased resistance to hydrogen peroxide-induced cardiac contracture is associated with decreased myocardial oxidative stress in hypothyroid rats. Cell Biochem Funct. 2010;28:38–44.PubMedCrossRefGoogle Scholar
  14. 14.
    Shinohara R, Mano T, Nagasaka A, Hayashi R, Uchimura K, Nakano I, Watanabe F, Tsugawa T, Makino M, Kakizawa H, Nagata M, Iwase K, Ishizuki Y, Itoh M. Lipid peroxidation levels in rat cardiac muscle are affected by age and thyroid status. J Endocrinol. 2000;164:97–102.PubMedCrossRefGoogle Scholar
  15. 15.
    Asayama K, Dobashi K, Hayashibe H, Megata Y, Kato K. Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rat: a possible mechanism of injury to heart and skeletal muscle in hyperthyroidism. Endocrinology. 1987;121:2112–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Bastug E, Tasliyurt T, Kutluturk F, Sahin S, Yilmaz A, Sivgin H, Yelken BM, Ozturk B, Yilmaz A, Sahin S. Evaluation of oxidative status with exhaled breath 8-isoprostane levels in patients with hyperthyroidism. Endocr Metab Immune Disord Drug Targets. 2013;13:306–10.PubMedCrossRefGoogle Scholar
  17. 17.
    Erem C, Suleyman AK, Civan N, Mentese A, Nuhoglu İ, Uzun A, Ersoz HO, Deger O. Ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hyperthyroidism: effects of treatment on oxidative stress. Endocr J. 2015;62:493–501.PubMedCrossRefGoogle Scholar
  18. 18.
    Cebeci E, Alibaz-Oner F, Usta M, Yurdakul S, Erguney M. Evaluation of oxidative stress, the activities of paraoxonase and arylesterase in patients with subclinical hypothyroidism. J Investig Med. 2012;60:23–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Reddy VS, Bukke S, Mahato K, Kumar V, Reddy NV, Munikumar M, Vodelu B. A meta-analysis of the association of serum ischaemia-modified albumin levels with human hypothyroidism and hyperthyroidism. Biosci Rep. 2017;37.Google Scholar
  20. 20.
    Erem C, Suleyman AK, Civan N, Mentese A, Nuhoglu İ, Uzun A, Coskun H, Deger O. The effect of L-thyroxine replacement therapy on ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hypothyroidism. Endocr Res. 2016;41:350–60.PubMedCrossRefGoogle Scholar
  21. 21.
    Cheserek MJ, Wu GR, Ntazinda A, Shi YH, Shen LY, Le GW. Association between thyroid hormones, lipids and oxidative stress markers in subclinical hypothyroidism. J Med Biochem. 2015;34:323–31.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Reddy VS, Gouroju S, Suchitra MM, Suresh V, Sachan A, Srinivasa Rao PV, Bitla AR. Antioxidant defense in overt and subclinical hypothyroidism. Horm Metab Res. 2013;45:754–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Öztürk Ü, Vural P, Özderya A, Karadağ B, Doğru-Abbasoğlu S, Uysal M. Oxidative stress parameters in serum and low density lipoproteins of Hashimoto’s thyroiditis patients with subclinical and overt hypothyroidism. Int Immunopharmacol. 2012;14:349–52.PubMedCrossRefGoogle Scholar
  24. 24.
    Pantos C, Mourouzis I. The emerging role of TRα1 in cardiac repair: potential therapeutic implications. Oxidative Med Cell Longev. 2014;2014:481482.CrossRefGoogle Scholar
  25. 25.
    Bengel FM, Nekolla SG, Ibrahim T, Weniger C, Ziegler SI, Schwaiger M. Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging. J Clin Endocrinol Metab. 2000;85:1822–7.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, Peeters R, Zaman A, Iervasi G. Thyroid hormones and cardiovascular function and diseases. J Am Coll Cardiol. 2018;71:1781–96.CrossRefGoogle Scholar
  27. 27.
    Mitchell JE, Hellkamp AS, Mark DB, Anderson J, Johnson GW, Poole JE, Lee KL, Bardy GH. Thyroid function in heart failure and impact on mortality. JACC Heart Fail. 2013;1:48–55.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116:1725–35.CrossRefGoogle Scholar
  29. 29.
    Asayama K, Kato K. Oxidative muscular injury and its relevance to hyperthyroidism. Free Radic Biol Med. 1990;8:293–303.PubMedCrossRefGoogle Scholar
  30. 30.
    Danzi S, Klein I. Thyroid disease and the cardiovascular system. Endocrinol Metab Clin N Am. 2014;43:517–28.CrossRefGoogle Scholar
  31. 31.
    Vargas-Uricoechea H, Bonelo-Perdomo A. Thyroid dysfunction and heart failure: mechanisms and associations. Curr Heart Fail Rep. 2017;14:48–58.PubMedCrossRefGoogle Scholar
  32. 32.
    Vargas-Uricoechea H, Sierra-Torres CH. Thyroid hormones and the heart. Horm Mol Biol Clin Invest. 2014;18:15–26.Google Scholar
  33. 33.
    Triggiani V, Iacoviello M. Thyroid disorders in chronic heart failure: from prognostic set-up to therapeutic management. Endocr Metab Immune Disord Drug Targets. 2013;13:22–37.PubMedCrossRefGoogle Scholar
  34. 34.
    Iervasi G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M, L’Abbate A, Donato L. Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation. 2003;107:708–13.CrossRefGoogle Scholar
  35. 35.
    Pingitore A, Galli E, Barison A, Iervasi A, Scarlattini M, Nucci D, L'abbate A, Mariotti R, Iervasi G. Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008;93:1351–8.CrossRefGoogle Scholar
  36. 36.
    Mitchell JE, Hellkamp AS, Mark DB, et al. Thyroid function in heart failure and impact on mortality. J Am Coll Cardiol HF. 2013;1:48–55.Google Scholar
  37. 37.
    Sabatino L, Iervasi G, Pingitore A. Thyroid hormone and heart failure: from myocardial protection to systemic regulation. Expert Rev Cardiovasc Ther. 2014;12:1227–36.CrossRefGoogle Scholar
  38. 38.
    Holmager P, Schmidt U, Mark P, Andersen U, Dominguez H, Raymond I, Zerahn B, Nygaard B, Kistorp C, Faber J. Long-term L-triiodothyronine (T3) treatment in stable systolic heart failure patients: a randomised, double-blind, cross-over, placebo-controlled intervention study. Clin Endocrinol. 2015;83:931–7.CrossRefGoogle Scholar
  39. 39.
    Amin A, Chitsazan M, Taghavi S, Ardeshiri M. Effects of triiodothyronine replacement therapy in patients with chronic stable heart failure and low-triiodothyronine syndrome: a randomized, double-blind, placebo-controlled study. ESC Heart Fail. 2015;2:5–11.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Degens H, Gilde AJ, Lindhout M, Willemsen PH, Van Der Vusse GJ, Van Bilsen M. Functional and metabolic adaptation of the heart to prolonged thyroid hormone treatment. Am J Physiol Heart Circ Physiol. 2003;284:H108–15.PubMedCrossRefGoogle Scholar
  41. 41.
    Mondal NK, Sorensen EN, Pham SM, Koenig SC, Griffith BP, Slaughter MS, Wu ZJ. Systemic inflammatory response syndrome in end-stage heart failure patients following continuous-flow left ventricular assist device implantation: differences in plasma redox status and leukocyte activation. Artif Organs. 2016;40:434–43.PubMedCrossRefGoogle Scholar
  42. 42.
    Wojciechowska C, Romuk E, Tomasik A, Skrzep-Poloczek B, Nowalany-Kozielska E, Birkner E, Jacheć W. Oxidative stress markers and C-reactive protein are related to severity of heart failure in patients with dilated cardiomyopathy. Mediat Inflamm. 2014;2014:147040.Google Scholar
  43. 43.
    Radovanovic S, Krotin M, Simic DV, Mimic-Oka J, Savic-Radojevic A, Pljesa-Ercegovac M, Matic M, Ninkovic N, Ivanovic B, Simic T. Markers of oxidative damage in chronic heart failure: role in disease progression. Redox Rep. 2008;1:109–16.CrossRefGoogle Scholar
  44. 44.
    Mallat Z, Philip I, Lebret M, Chatel D, Maclouf J, Tedgui A. Elevated levels of 8-iso-prostaglandin F2alpha in pericardial fluid of patients with heart failure: a potential role for in vivo oxidant stress in ventricular dilatation and progression to heart failure. Circulation. 1998;97:1536–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Wolfram R, Oguogho A, Palumbo B, Sinzinger H. Enhanced oxidative stress in coronary heart disease and chronic heart failure as indicated by an increased 8-epi-PGF (2alpha). Eur J Heart Fail. 2005;7:167–72.PubMedCrossRefGoogle Scholar
  46. 46.
    Tingberg E, Ohlin AK, Gottsäter A, Ohlin H. Lipid peroxidation is not increased in heart failure patients on modern pharmacological therapy. Int J Cardiol. 2006;112:275–81.PubMedCrossRefGoogle Scholar
  47. 47.
    Zia AA, Komolafe BO, Moten M, Ahokas RA, McGee JE, William Rosenberg E, Bhattacharya SK, Weber KT. Supplemental vitamin D and calcium in the management of African Americans with heart failure having hypovitaminosis D. Am J Med Sci. 2011;341:113–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A, Omran AS, Jeejeebhoy KN. Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol. 1998;31:1352–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Di Minno A, Turnu L, Porro B, Squellerio I, Cavalca V, Tremoli E, Di Minno MN. 8-Hydroxy-2-deoxyguanosine levels and heart failure: a systematic review and meta-analysis of the literature. Nutr Metab Cardiovasc Dis. 2017;27:201–8.PubMedCrossRefGoogle Scholar
  50. 50.
    de Meirelles LR, Resende Ade C, Matsuura C, Salgado A, Pereira NR, Cascarelli PG, Mendes-Ribeiro AC, Brunini TM. Platelet activation, oxidative stress and overexpression of inducible nitric oxide synthase in moderate heart failure. Clin Exp Pharmacol Physiol. 2011;38:705–10.PubMedCrossRefGoogle Scholar
  51. 51.
    Sheeran FL, Pepe S. Mitochondrial bioenergetics and dysfunction in failing heart. Adv Exp Med Biol. 2017;982:65–80.PubMedCrossRefGoogle Scholar
  52. 52.
    Perrotta C, De Palma C, Falcone S, Sciorati C, Clementi E. Nitric oxide, ceramide and sphingomyelinase-coupled receptors: a tale of enzymes and messengers coordinating cell death, survival and differentiation. Life Sci. 2005;77:1732–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Kogot-Levin A, Saada A. Ceramide and the mitochondrial respiratory chain. Biochimie. 2014;100:88–94.PubMedCrossRefGoogle Scholar
  54. 54.
    Zigdon H, Kogot-Levin A, Park JW, Goldschmidt R, Kelly S, Merrill AH Jr, Scherz A, Pewzner-Jung Y, Saada A, Futerman AH. Ablation of ceramide synthase 2 causes chronic oxidative stress due to disruption of the mitochondrial respiratory chain. J Biol Chem. 2013;288:4947–56.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Peterson LR, Xanthakis V, Duncan MS, Gross S, Friedrich N, Völzke H, Felix SB, Jiang H, Sidhu R, Nauck M, Jiang X, Ory DS, Dörr M, Vasan RS, Schaffer JE. Ceramide remodeling and risk of cardiovascular events and mortality. J Am Heart Assoc. 2018;7.Google Scholar
  56. 56.
    Reichlin T, Socrates T, Egli P, Potocki M, Breidthardt T, Arenja N, Meissner J, Noveanu M, Reiter M, Twerenbold R, Schaub N, Buser A, Mueller C. Use of myeloperoxidase for risk stratification in acute heart failure. Clin Chem. 2010;56:944–51.PubMedCrossRefGoogle Scholar
  57. 57.
    Tang WH, Katz R, Brennan ML, Aviles RJ, Tracy RP, Psaty BM, Hazen SL. Usefulness of myeloperoxidase levels in healthy elderly subjects to predict risk of developing heart failure. Am J Cardiol. 2009;103:1269–74.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Radovanovic S, Savic-Radojevic A, Pljesa-Ercegovac M, Djukic T, Suvakov S, Krotin M, Simic DV, Matic M, Radojicic Z, Pekmezovic T, Simic T. Markers of oxidative damage and antioxidant enzyme activities as predictors of morbidity and mortality in patients with chronic heart failure. J Card Fail. 2012;18:493–501.PubMedCrossRefGoogle Scholar
  59. 59.
    Askari H, Rajani SF, Poorebrahim M, Haghi-Aminjan H, Raeis-Abdollahi E, Abdollahi M. A glance at the therapeutic potential of irisin against diseases involving inflammation, oxidative stress, and apoptosis: an introductory review. Pharmacol Res. 2018;129:44–55.PubMedCrossRefGoogle Scholar
  60. 60.
    Hsieh IC, Ho MY, Wen MS, Chen CC, Hsieh MJ, Lin CP, Yeh JK, Tsai ML, Yang CH, Wu VC, Hung KC, Wang CC, Wang CY. Serum irisin levels are associated with adverse cardiovascular outcomes in patients with acute myocardial infarction. Int J Cardiol. 2018;261:12–7.PubMedCrossRefGoogle Scholar
  61. 61.
    White M, Ducharme A, Ibrahim R, Whittom L, Lavoie J, Guertin MC, Racine N, He Y, Yao G, Rouleau JL, Schiffrin EL, Touyz RM. Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: improvement after short-term inotropic support. Clin Sci (Lond). 2006;110:483–9.CrossRefGoogle Scholar
  62. 62.
    Katsiki N, Doumas M, Mikhailidis DP. Lipids, statins and heart failure: an update. Curr Pharm Des. 2016;22:4796–806.PubMedCrossRefGoogle Scholar
  63. 63.
    Nakamura K, Murakami M, Miura D, Yunoki K, Enko K, Tanaka M, Saito Y, Nishii N, Miyoshi T, Yoshida M, Oe H, Toh N, Nagase S, Kohno K, Morita H, Matsubara H, Kusano KF, Ohe T, Ito H. Beta-blockers and oxidative stress in patients with heart failure. Pharmaceuticals (Basel). 2011;4:1088–100.CrossRefGoogle Scholar
  64. 64.
    Vanzelli AS, Medeiros A, Rolim N, Bartholomeu JB, Cunha TF, Bechara LR, Gomes ER, Mattos KC, Sirvente R, Salemi VM, Mady C, Negrao CE, Guatimosim S, Brum PC. Integrative effect of carvedilol and aerobic exercise training therapies on improving cardiac contractility and remodeling in heart failure mice. PLoS One. 2013;8:e62452.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Rehsia NS, Dhalla NS. Mechanisms of the beneficial effects of beta-adrenoceptor antagonists in congestive heart failure. Exp Clin Cardiol. 2010;15:e86–95.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Le DE, Pascotto M, Leong-Poi H, Sari I, Micari A, Kaul S. Anti-inflammatory and pro-angiogenic effects of beta blockers in a canine model of chronic ischemic cardiomyopathy: comparison between carvedilol and metoprolol. Basic Res Cardiol. 2013;108:384.PubMedCrossRefGoogle Scholar
  67. 67.
    Park M, Steinberg SF. Carvedilol prevents redox inactivation of cardiomyocyte Β(1)-adrenergic receptors. JACC Basic Transl Sci. 2018;3:521–32.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Kono Y, Nakamura K, Kimura H, Nishii N, Watanabe A, Banba K, Miura A, Nagase S, Sakuragi S, Kusano KF, Matsubara H, Ohe T. Elevated levels of oxidative DNA damage in serum and myocardium of patients with heart failure. Circ J. 2006;70:1001–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Parissis JT, Andreadou I, Bistola V, Paraskevaidis I, Filippatos G, Kremastinos DT. Novel biologic mechanisms of levosimendan and its effect on the failing heart. Expert Opin Investig Drugs. 2008;17:1143–50.PubMedCrossRefGoogle Scholar
  70. 70.
    Parissis JT, Andreadou I, Markantonis SL, Bistola V, Louka A, Pyriochou A, Paraskevaidis I, Filippatos G, Iliodromitis EK, Kremastinos DT. Effects of levosimendan on circulating markers of oxidative and nitrosative stress in patients with advanced heart failure. Atherosclerosis. 2007;195:e210–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Adam M, Meyer S, Knors H, Klinke A, Radunski UK, Rudolph TK, Rudolph V, Spin JM, Tsao PS, Costard-Jäckle A, Baldus S. Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure. Sci Rep. 2015;5:9704.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Bhatt KN, Butler J. Myocardial energetics and heart failure: a review of recent therapeutic trials. Curr Heart Fail Rep. 2018;15:191–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Campos JC, Queliconi BB, Bozi LHM, Bechara LRG, Dourado PMM, Andres AM, Jannig PR, Gomes KMS, Zambelli VO, Rocha-Resende C, Guatimosim S, Brum PC, Mochly-Rosen D, Gottlieb RA, Kowaltowski AJ, Ferreira JCB. Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure. Autophagy. 2017;13:1304–17.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Sties SW, Andreato LV, de Carvalho T, Gonzáles AI, Angarten VG, Ulbrich AZ, de Mara LS, Netto AS, da Silva EL, Andrade A. Influence of exercise on oxidative stress in patients with heart failure. Heart Fail Rev. 2018;23:225–35.PubMedCrossRefGoogle Scholar
  75. 75.
    Kiyuna LA, Prestes E, Albuquerque R, Chen CH, Mochly-Rosen D, Ferreira JCB. Targeting mitochondrial dysfunction and oxidative stress in heart failure: challenges and opportunities. Free Radic Biol Med. 2018;129:155–68.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Dos Reis Padilha G, Sanches Machado d’Almeida K, Ronchi Spillere S, Corrêa Souza G. Dietary patterns in secondary prevention of heart failure: a systematic review. Nutrients. 2018;10.PubMedCentralCrossRefPubMedGoogle Scholar
  77. 77.
    Vassalle C. New biomarkers and traditional cardiovascular risk scores: any crystal ball for current effective advice and future exact prediction? Clin Chem Lab Med. 2018;56:1803–5.PubMedCrossRefGoogle Scholar
  78. 78.
    Izumiya Y, Hanatani S, Kimura Y, Takashio S, Yamamoto E, Kusaka H, Tokitsu T, Rokutanda T, Araki S, Tsujita K, Tanaka T, Yamamuro M, Kojima S, Tayama S, Kaikita K, Hokimoto S, Ogawa H. Growth differentiation factor-15 is a useful prognostic marker in patients with heart failure with preserved ejection fraction. Can J Cardiol. 2014;30:338–44.PubMedCrossRefGoogle Scholar
  79. 79.
    Dupuy AM, Kuster N, Curinier C, Huet F, Plawecki M, Solecki K, Roubille F, Cristol JP. Exploring collagen remodeling and regulation as prognosis biomarkers in stable heart failure. Clin Chim Acta. 2018; pii: S0009-8981:30459-5.Google Scholar
  80. 80.
    Sobrino-Márquez JM, Grande-Trillo A, Cantero-Pérez EM, Rangel-Sousa D, Lage-Galle E, Adsuar-Gómez A. Prognostic value of blood panel parameters in patients with dilated cardiomyopathy and advanced heart failure. Transplant Proc. 2018;50:650–2.PubMedCrossRefGoogle Scholar
  81. 81.
    Bahrmann P, Bahrmann A, Hofner B, Christ M, Achenbach S, Sieber CC, Bertsch T. Multiple biomarker strategy for improved diagnosis of acute heart failure in older patients presenting to the emergency department. Eur Heart J Acute Cardiovasc Care. 2015;4:137–47.PubMedCrossRefGoogle Scholar
  82. 82.
    Bjurman C, Holmström A, Petzold M, Hammarsten O, Fu ML. Assessment of a multi-marker risk score for predicting cause-specific mortality at three years in older patients with heart failure and reduced ejection fraction. Cardiol J. 2015;22:31–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Ng LL, Pathik B, Loke IW, Squire IB, Davies JE. Myeloperoxidase and C-reactive protein augment the specificity of B-type natriuretic peptide in community screening for systolic heart failure. Am Heart J. 2006;152:94–101.PubMedCrossRefGoogle Scholar
  84. 84.
    O’Donoghue ML, Morrow DA, Cannon CP, Jarolim P, Desai NR, Sherwood MW, Murphy SA, Gerszten RE, Sabatine MS. Multimarker risk stratification in patients with acute myocardial infarction. J Am Heart Assoc. 2016;5.Google Scholar
  85. 85.
    Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB, Anand I, Maggioni A, Burton P, Sullivan MD, Pitt B, Poole-Wilson PA, Mann DL, Packer M. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation. 2006;113:1424–33.PubMedCrossRefGoogle Scholar
  86. 86.
    Katz MG, Fargnoli AS, Williams RD, Kendle AP, Steuerwald NM, Bridges CR. MiRNAs as potential molecular targets in heart failure. Futur Cardiol. 2014;10:789–800.CrossRefGoogle Scholar
  87. 87.
    Fuschi P, Carrara M, Voellenkle C, Garcia-Manteiga JM, Righini P, Maimone B, Sangalli E, Villa F, Specchia C, Picozza M, Nano G, Gaetano C, Spinetti G, Puca AA, Magenta A, Martelli F. Central role of the p53 pathway in the noncoding-RNA response to oxidative stress. Aging (Albany NY). 2017;9:2559–86.CrossRefGoogle Scholar
  88. 88.
    Gurha P, Wang T, Larimore AH, Sassi Y, Abreu-Goodger C, Ramirez MO, Reddy AK, Engelhardt S, Taffet GE, Wehrens XH, Entman ML, Rodriguez A. microRNA-22 promotes heart failure through coordinate suppression of PPAR/ERR-nuclear hormone receptor transcription. PLoS One. 2013;8:e75882.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Wang X, Song C, Zhou X, Han X, Li J, Wang Z, Shang H, Liu Y, Cao H. Mitochondria associated microRNA expression profiling of heart failure. Biomed Res Int. 2017;2017:4042509.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Liu X, Tong Z, Chen K, Hu X, Jin H, Hou M. The role of miRNA-132 against apoptosis and oxidative stress in heart failure. Biomed Res Int. 2018;2018:3452748.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Olson EN. MicroRNAs as therapeutic targets and biomarkers of cardiovascular disease. Sci Transl Med. 2014;6:239ps3.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Dirkx E, Gladka MM, Philippen LE, Armand AS, Kinet V, Leptidis S, El Azzouzi H, Salic K, Bourajjaj M, da Silva GJ, Olieslagers S, van der Nagel R, de Weger R, Bitsch N, Kisters N, Seyen S, Morikawa Y, Chanoine C, Heymans S, Volders PG, Thum T, Dimmeler S, Cserjesi P, Eschenhagen T, da Costa Martins PA, De Windt LJ. Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. Nat Cell Biol. 2013;15:1282–93.PubMedCrossRefGoogle Scholar
  93. 93.
    Wahlquist C, Jeong D, Rojas-Muñoz A, Kho C, Lee A, Mitsuyama S, van Mil A, Park WJ, Sluijter JP, Doevendans PA, Hajjar RJ, Mercola M. Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature. 2014;508:531–5.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, Castoldi M, Soutschek J, Koteliansky V, Rosenwald A, Basson MA, Licht JD, Pena JT, Rouhanifard SH, Muckenthaler MU, Tuschl T, Martin GR, Bauersachs J, Engelhardt S. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980–4.CrossRefGoogle Scholar
  95. 95.
    Patrick DM, Montgomery RL, Qi X, Obad S, Kauppinen S, Hill JA, van Rooij E, Olson EN. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. J Clin Invest. 2010;120:3912–6.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    de Castro AL, Tavares AV, Campos C, Fernandes RO, Siqueira R, Conzatti A, Bicca AM, Fernandes TR, Sartório CL, Schenkel PC, Belló-Klein A, da Rosa Araujo AS. Cardioprotective effects of thyroid hormones in a rat model of myocardial infarction are associated with oxidative stress reduction. Mol Cell Endocrinol. 2014;391:22–9.CrossRefGoogle Scholar
  97. 97.
    de Castro AL, Tavares AV, Fernandes RO, Campos C, Conzatti A, Siqueira R, Fernandes TR, Schenkel PC, Sartório CL, Llesuy S, Belló-Klein A, da Rosa Araujo AS. T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats. Mol Cell Biochem. 2015;408:235–43.CrossRefGoogle Scholar
  98. 98.
    Ghosh G, De K, Maity S, Bandyopadhyay D, Bhattacharya S, Reiter RJ, Bandyopadhyay A. Melatonin protects against oxidative damage and restores expression of GLUT4 gene in the hyperthyroid rat heart. J Pineal Res. 2007;42:71–82.PubMedCrossRefGoogle Scholar
  99. 99.
    de Lorgeril M, Salen P. Selenium and antioxidant defenses as major mediators in the development of chronic heart failure. Heart Fail Rev. 2006;11:13–7.PubMedCrossRefGoogle Scholar
  100. 100.
    Metes-Kosik N, Luptak I, Dibello PM, Handy DE, Tang SS, Zhi H, Qin F, Jacobsen DW, Loscalzo J, Joseph J. Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance. Mol Nutr Food Res. 2012;56:1812–24.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Wu HY, Xia YM, Ha PC, Chen XS. Changes in myocardial thyroid hormone metabolism and alpha-glycerophosphate dehydrogenase activity in rats deficient in iodine and selenium. Br J Nutr. 1997;78:671–6.PubMedCrossRefGoogle Scholar
  102. 102.
    McKeag NA, McKinley MC, Woodside JV, Harbinson MT, McKeown PP. The role of micronutrients in heart failure. J Acad Nutr Diet. 2012;112:870–86.PubMedCrossRefGoogle Scholar
  103. 103.
    Vassalle C, Maffei S, Iervasi G. Bone remodelling biomarkers: new actors on the old cardiovascular stage. “Biomarker validation—technological, clinical and commercial aspects” Ed Wiley-VCH Verlag GmbH & Co. KGaA, Published Online: 27 Feb 2015, Chapter 7, pp. 107–46. Print ISBN: 9783527337194. Online ISBN: 9783527680658. Scholar
  104. 104.
    Koch A, Grammatikos G, Trautmann S, Schreiber Y, Thomas D, Bruns F, Pfeilschifter J, Badenhoop K, Penna-Martinez M. Vitamin D supplementation enhances C18(dihydro)ceramide levels in type 2 diabetes patients. Int J Mol Sci. 2017;18.PubMedCentralCrossRefPubMedGoogle Scholar
  105. 105.
    Liu Z, Ren Z, Zhang J, Chuang CC, Kandaswamy E, Zhou T, Zuo L. Role of ROS and nutritional antioxidants in human diseases. Front Physiol. 2018;9:477.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Moretti HD, Colucci VJ, Berry BD. Vitamin D(3) repletion versus placebo as adjunctive treatment of heart failure patient quality of life and hormonal indices: a randomized, double-blind, placebo-controlled trial. BMC Cardiovasc Disord. 2017;17:274.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Belen E, Tipi FF, Aykan AC, Findikçioğlu U, Karakuş G, Yeşil A, Helvaci A, Kalaycioğlu E, Cetin M. Clinical staging in chronic heart failure associated with low vitamin D and elevated parathormone levels. Acta Cardiol. 2014;69:665–71.PubMedCrossRefGoogle Scholar
  108. 108.
    Gouveia CH, Christoffolete MA, Zaitune CR, Dora JM, Harney JW, Maia AL, Bianco AC. Type 2 iodothyronine selenodeiodinase is expressed throughout the mouse skeleton and in the MC3T3-E1 mouse osteoplastic cell line during differentiation. Endocrinology. 2005;146:195–200.PubMedCrossRefGoogle Scholar
  109. 109.
    Alrefaie Z, Awad H. Effect of vitamin D3 on thyroid function and deiodinase 2 expression in diabetic rats. Arch Physiol Biochem. 2015;121:206–9.CrossRefGoogle Scholar
  110. 110.
    Miura M, Tanaka K, Komatsu Y, Suda M, Yasoda A, Sakuma Y, Ozasa A, Nakao K. A novel interaction between thyroid hormones and 1,25(OH)(2)D(3) in osteoclast formation. Biochem Biophys Res Commun. 2002;291:987–94.PubMedCrossRefGoogle Scholar
  111. 111.
    Jabbar A, Pingitore A, Pearce SH, Zaman A, Iervasi G, Razvi S. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol. 2017;14:39–55.CrossRefGoogle Scholar
  112. 112.
    Vassalle C. Oxidative stress and cardiovascular risk prediction: the long way towards a “radical” perspective. Int J Cardiol. 2018;273:252–3.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Melania Gaggini
    • 1
  • Irene Traghella
    • 2
  • Cristina Vassalle
    • 2
    Email author
  1. 1.Istituto di Fisiologia Clinica, CNRPisaItaly
  2. 2.Fondazione G. Monasterio CNR Regione ToscanaPisaItaly

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