Skip to main content

Thyroid Hormone, Mitochondrial Function and Cardioprotection

  • Chapter
  • First Online:
Book cover Thyroid and Heart

Abstract

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Existing therapies provide symptomatic and clinical benefit but do not fully address the molecular abnormalities that affect the injured cardiomyocytes. Alterations in mitochondrial function are increasingly recognized to play a key pathogenic role in acute myocardial infarction and in chronic CVD. Mitochondrial dysfunctions in CVD include impaired electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. Recent understanding of the complex interaction between thyroid hormone signaling and microRNAs in the regulation of mitochondria quality control and cell fate can provide novel insights and therapeutic targets. The purpose of this chapter is to illustrate the cardioprotective effects of TH against the exasperation of CVD such as ischemia/reperfusion injury and heart failure, focusing on mitochondrial function and quality control. To this aim, we summarize the main tasks that mitochondria manage in cardiovascular physiology and disease and provide insight into how a myocardial low T3 state may contribute to mitochondrial defects and fibrosis/death axis leading to CVD progression. The beneficial effects of a TH replacement therapy on key mitochondrial pathways implicated in CVD are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Huss JM, Kelly DP. Mitochondrial energy metabolism in heart failure: a question of balance. J Clin Invest. 2005;115:547–55. https://doi.org/10.1172/JCI24405.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Carley AN, Taegtmeyer H, Lewandowski ED. Mechanisms linking energy substrate metabolism to the function of the heart. Circ Res. 2014;114(4):717–29. https://doi.org/10.1161/CIRCRESAHA.114.301863.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Suliman HB, Piantadosi CA. Mitochondrial quality control as a therapeutic target. Pharmacol Rev. 2016;68:20–48. https://doi.org/10.1124/pr.115.011502.

    Article  PubMed  CAS  Google Scholar 

  4. Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL. Mitochondrial dysfunction in cardiac disease: ischemia-reperfusion, aging, and heart failure. J Mol Cell Cardiol. 2001;33(6):1065–89. https://doi.org/10.1006/jmcc.2001.1378.

    Article  PubMed  CAS  Google Scholar 

  5. Marín-García J, Goldenthal MJ. Mitochondrial centrality in heart failure. Heart Fail Rev. 2008;13:137–50. https://doi.org/10.1007/s10741-007-9079-1.

    Article  PubMed  Google Scholar 

  6. Neubauer S. The failing heart-an engine out of fuel. N Engl J Med. 2007;356:1140–51. https://doi.org/10.1056/NEJMra063052.

    Article  PubMed  Google Scholar 

  7. Di Lisa F, Canton M, Menabò R, Kaludercic N, Bernardi P. Mitochondria and cardioprotection. Heart Fail Rev. 2007;12(3–4):249–60. https://doi.org/10.1007/s10741-007-9028-z.

    Article  PubMed  CAS  Google Scholar 

  8. Bonora M, Wieckowski MR, Sinclair DA, Kroemer G, Pinton P, Galluzzi L. Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles. Nat Rev Cardiol. 2018;16:33–55. https://doi.org/10.1038/s41569-018-0074-0.

    Article  CAS  Google Scholar 

  9. Wrutniak-Cabello C, Casas F, Cabello G. Thyroid hormone action in mitochondria. J Mol Endocrinol. 2001;26:67–77. https://doi.org/10.1677/jme.0.0260067.

    Article  PubMed  CAS  Google Scholar 

  10. Goldenthal MJ, Ananthakrishnan R, Marín-García J. Nuclear-mitochondrial cross-talk in cardiomyocyte T3 signaling: a time-course analysis. J Mol Cell Cardiol. 2005;39:319–26. https://doi.org/10.1016/j.yjmcc.2005.03.016.

    Article  PubMed  CAS  Google Scholar 

  11. Marín-García J. Thyroid hormone and myocardial mitochondrial biogenesis. Vasc Pharmacol. 2010;52:120–30. https://doi.org/10.1016/j.vph.2009.10.008.

    Article  CAS  Google Scholar 

  12. Cioffi F, Senese R, Lanni A, Goglia F. Thyroid hormones and mitochondria: with a brief look at derivatives and analogues. Mol Cell Endocrinol. 2013;379(1–2):51–61. https://doi.org/10.1016/j.mce.2013.06.006.

    Article  PubMed  CAS  Google Scholar 

  13. Forini F, Nicolini G, Iervasi G. Mitochondria as key targets of cardioprotection in cardiac ischemic disease: role of thyroid hormone triiodothyronine. Int J Mol Sci. 2015;16(3):6312–36. https://doi.org/10.3390/ijms16036312.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Forini F, Lionetti V, Ardehali H, Pucci A, Cecchetti F, Ghanefar M, et al. Early long-term L-T3 replacement rescues mitochondria and prevents ischemic cardiac remodeling in rats. J Cell Mol Med. 2011;15(3):514–24. https://doi.org/10.1111/j.1582-4934.2010.01014.x.

    Article  PubMed  CAS  Google Scholar 

  15. Forini F, Ucciferri N, Kusmic C, Nicolini G, Cecchettini A, Rocchiccioli S, et al. Low T3 state is correlated with cardiac mitochondrial impairments after ischemia reperfusion injury: evidence from a proteomic approach. Int J Mol Sci. 2015;16(11):26687–705. https://doi.org/10.3390/ijms161125973.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Forini F, Kusmic C, Nicolini G, Mariani L, Zucchi R, Matteucci M, et al. Triiodothyronine prevents cardiac ischemia/reperfusion mitochondrial impairment and cell loss by regulating miR30a/p53 axis. Endocrinology. 2014;155(11):4581–90. https://doi.org/10.1210/en.2014-1106.

    Article  PubMed  CAS  Google Scholar 

  17. Forini F, Nicolini G, Kusmic C, D’Aurizio R, Rizzo M, Baumgart M, et al. Integrative analysis of differentially expressed genes and miRNAs predicts complex T3-mediated protective circuits in a rat model of cardiac ischemia reperfusion. Sci Rep. 2018;8(1):13870. https://doi.org/10.1038/s41598-018-32237-0.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hyyti OM, Ning XH, Buroker NE, Ge M, Portman MA. Thyroid hormone controls myocardial substrate metabolism through nuclear receptor-mediated and rapid posttranscriptional mechanisms. Am J Physiol Endocrinol Metab. 2006;290(2):E372–9. https://doi.org/10.1152/ajpendo.00288.2005.

    Article  PubMed  CAS  Google Scholar 

  19. Kolwicz SC Jr, Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res. 2013;113(5):603–16. https://doi.org/10.1161/CIRCRESAHA.113.302095.

    Article  PubMed  CAS  Google Scholar 

  20. Ingwall JS. Energy metabolism in heart failure and remodeling. Cardiovasc Res. 2009;81:412–9. https://doi.org/10.1093/cvr/cvn301.

    Article  PubMed  CAS  Google Scholar 

  21. Ardehali H, Sabbah HN, Burke MA, Sarma S, Liu PP, Cleland JG, et al. Targeting myocardial substrate metabolism in heart failure: potential for new therapies. Eur J Heart Fail. 2012;14:120–9. https://doi.org/10.1093/eurjhf/hfr173.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Tuunanen H, Engblom E, Naum A, Någren K, Hesse B, Airaksinen KE, et al. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation. 2006;114:2130–7. https://doi.org/10.1161/CIRCULATIONAHA.106.645184.

    Article  PubMed  CAS  Google Scholar 

  23. Abdurrachim D, Luiken JJ, Nicolay K, Glatz JF, Prompers JJ, Nabben M. Good and bad consequences of altered fatty acid metabolism in heart failure: evidence from mouse models. Cardiovasc Res. 2015;106(2):194–205. https://doi.org/10.1093/cvr/cvv105.

    Article  PubMed  CAS  Google Scholar 

  24. Haynie KR, Vandanmagsar B, Wicks SE, Zhang J, Mynat RL. Inhibition of carnitine palymitoyltransferase1b induces cardiac hypertrophy and mortality in mice. Diabetes Obes Metab. 2014;16(8):757–60. https://doi.org/10.1111/dom.12248.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. He L, Kim T, Long Q, Liu J, Wang P, Zhou Y, et al. Carnitine palmitoyltransferase-1b deficiency aggravates pressure overload-induced cardiac hypertrophy caused by lipotoxicity. Circulation. 2012;126:1705–16. https://doi.org/10.1161/CIRCULATIONAHA.111.075978.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Ledee D, Portman MA, Kajimoto M, Isern N, Olson AK. Thyroid hormone reverses aging-induced myocardial fatty acid oxidation defects and improves the response to acutely increased afterload. PLoS One. 2013;8(6):e65532. https://doi.org/10.1371/journal.pone.0065532.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Liu Q, Clanachan AS, Lopaschuk GD. Acute effects of triiodothyronine on glucose and fatty acid metabolism during reperfusion of ischemic rat hearts. Am J Physiol Endocrinol Metab. 1998;275:E392–9.

    Article  CAS  Google Scholar 

  28. Scholz TD, TenEyck CJ, Schutte BC. Thyroid hormone regulation of the NADH shuttles in liver and cardiac mitochondria. J Mol Cell Cardiol. 2000;32:1–10. https://doi.org/10.1006/jmcc.1999.1047.

    Article  PubMed  CAS  Google Scholar 

  29. Ralphe JC, Bedell K, Segar JL, Scholz TD. Correlation between myocardial malate/aspartate shuttle activity and EAAT1 protein expression in hyper- and hypothyroidism. Am J Physiol Heart Circ Physiol. 2005;288:H2521–6.

    Article  CAS  Google Scholar 

  30. Lewandowski ED, White LT. Pyruvate dehydrogenase influences postischemic heart function. Circulation. 1995;91:2071–9.

    Article  CAS  Google Scholar 

  31. Barak C, Reed MK, Maniscalco SP, Sherry AD, Malloy CR, Jessen ME. Effects of dichloroacetate on mechanical recovery and oxidation of physiologic substrates after ischemia and reperfusion in the isolated heart. J Cardiovasc Pharmacol. 1998;31(3):336–4.

    Article  CAS  Google Scholar 

  32. Hermann HP, Pieske B, Schwarzmüller E, Keul J, Just H, Hasenfuss G. Haemodynamic effects of intracoronary pyruvate in patients with congestive heart failure: an open study. Lancet. 1999;353:1321–3.

    Article  CAS  Google Scholar 

  33. Gevi F, Campolo F, Naro F, Zolla L. The cardioprotective effect of sildenafil is mediated by the activation of malate dehydrogenase and an increase in the malate-aspartate shuttle in cardiomyocytes. Biochem Pharmacol. 2017;127:60–70. https://doi.org/10.1016/j.bcp.2016.12.017.

    Article  PubMed  CAS  Google Scholar 

  34. Young VR, Ajami AM. Glutamate: an amino acid of particular distinction. J Nutr. 2000;130:892S–900S. https://doi.org/10.1093/jn/130.4.892S.

    Article  PubMed  CAS  Google Scholar 

  35. Kimose HH, Helligsø P, Randsbaek F, Kim Y, Bøtker HE, Hansen SB, et al. Improved recovery after cold crystalloid cardioplegia using low-dose glutamate enrichment during reperfusion after aortic unclamping: a study in isolated blood-perfused pig hearts. Thorac Cardiovasc Surg. 1996;44:118–25.

    Article  CAS  Google Scholar 

  36. Pereda D, Castella M, Pomar JL, Cartaña R, Josa M, Barriuso C, et al. Elective cardiac surgery using Celsior or St. Thomas No. 2 solution: a prospective, single-center, randomized pilot study. Eur J Cardiothorac Surg. 2007;32:501–6. https://doi.org/10.1016/j.ejcts.2007.05.021.

    Article  PubMed  Google Scholar 

  37. Beeckmans S, Kanarek L. Demonstration of physical interactions between consecutive enzymes of the citric acid cycle and of the aspartate-malate shuttle. A study involving fumarase, malate dehydrogenase, citrate synthesis and aspartate aminotransferase. Eur J Biochem. 1981;117:527–35.

    Article  CAS  Google Scholar 

  38. King N, Lin H, McGivan JD, Suleiman MS. Aspartate transporter expression and activity in hypertrophic rat heart and ischaemia–reperfusion injury. J Physiol. 2004;556(3):849–58.

    Article  CAS  Google Scholar 

  39. Nielsen TT, Støttrup NB, Løfgren B, Bøtker HE. Metabolic fingerprint of ischaemic cardioprotection: importance of the malate-aspartate shuttle. Cardiovasc Res. 2011;91(3):382–91. https://doi.org/10.1093/cvr/cvr051.

    Article  PubMed  CAS  Google Scholar 

  40. Fowler ED, Benoist D, Drinkhill MJ, Stones R, Helmes M, Wüst RC, et al. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension. J Mol Cell Cardiol. 2015;86:1–8. https://doi.org/10.1016/j.yjmcc.2015.06.016.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Weiss RG, Gerstenblith G, Bottomley PA. ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci U S A. 2005;102(3):808–13.

    Article  CAS  Google Scholar 

  42. Bottomley PA, Panjrath GS, Lai S, Hirsch GA, Wu K, Najjar SS, et al. Metabolic rates of ATP transfer through creatine kinase (CK flux) predict clinical heart failure events and death. Sci Transl Med. 2013;5(215):215re3. https://doi.org/10.1126/scitranslmed.3007328.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Madathil A, Hollingsworth KG, Blamire AM, Razvi S, Newton JL, Taylor R, et al. Levothyroxine improves abnormal cardiac bioenergetics in subclinical hypothyroidism: a cardiac magnetic resonance spectroscopic study. J Clin Endocrinol Metab. 2015;100(4):E607–10. https://doi.org/10.1210/jc.2014-2942.

    Article  PubMed  CAS  Google Scholar 

  44. Kajimoto M, Priddy CM, Ledee DR, Xu C, Isern N, Olson AK, et al. Effects of continuous triiodothyronine infusion on the tricarboxylic acid cycle in the normal immature swine heart under extracorporeal membrane oxygenation in vivo. Am J Physiol Heart Circ Physiol. 2014;306(8):H1164–70. https://doi.org/10.1152/ajpheart.00964.2013.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Luo M, Anderson ME. Ca2+ cycling in heart failure. Circ Res. 2013;113(6):690–708. https://doi.org/10.1161/CIRCRESAHA.113.301651.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Kawase Y, Hajjar RJ. The cardiac sarcoplasmic/endoplasmic reticulum calcium ATPase: a potent target for cardiovascular diseases. Nat Clin Pract Cardiovasc Med. 2008;5:554–65. https://doi.org/10.1038/ncpcardio1301.

    Article  PubMed  CAS  Google Scholar 

  47. de Oliveira Faria T, Costa GP, Almenara CCP, Angeli JK, Vassallo DV, Stefanon I, et al. Chronic exposure to low doses of HgCl2 avoids calcium handling impairment in the right ventricle after myocardial infarction in rats. PLoS One. 2014;9(4):e95639. https://doi.org/10.1371/journal.pone.00956398.

    Article  Google Scholar 

  48. Kawase Y, Ly HQ, Prunier F, Lebeche D, Shi Y, Jin H, et al. Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure. J Am Coll Cardiol. 2008;51:1112–9. https://doi.org/10.1016/j.jacc.2007.12.014.

    Article  PubMed  CAS  Google Scholar 

  49. Lipskaia L, Hadri L, Lopez JJ, Hajjar RJ, Bobe R. Benefit of SERCA2a gene transfer to vascular endothelial and smooth muscle cells: a new aspect in therapy of cardiovascular diseases. Curr Vasc Pharmacol. 2013;11(4):465–79.

    Article  CAS  Google Scholar 

  50. O’Donnell JM, Pound K, Xu X, Lewandowski ED. SERCA1 expression enhances the metabolic efficiency of improved contractility in post-ischemic heart. J Mol Cell Cardiol. 2009;47(5):614–21. https://doi.org/10.1016/j.yjmcc.2009.08.031.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Reed TD, Babu GJ, Ji Y, Zilberman A, Heyen MV, Wuytack F. The expression of SR calcium transport ATPase and the Na+/Ca2+ exchanger are antithetically regulated during mouse cardiac development and in hypo/hyperthyroidism. J Mol Cell Cardiol. 2000;32(3):453–64. https://doi.org/10.1006/jmcc.1999.1095.

    Article  PubMed  CAS  Google Scholar 

  52. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116:1725–35. https://doi.org/10.1161/CIRCULATIONAHA.106.678326.

    Article  PubMed  Google Scholar 

  53. Kahali GJ, Dillmann WH. Thyroid hormone action in the heart. Endocr Rev. 2005;26(5):704–28. https://doi.org/10.1210/er.2003-0033.

    Article  CAS  Google Scholar 

  54. Kiss E, Jakab G, Kranias EG, Edes I. Thyroid hormone-induced alterations in phospholamban protein expression: regulatory effects on sarcoplasmic reticulum Ca2+ transport and myocardial relaxation. Circ Res. 1994;75:245–51.

    Article  CAS  Google Scholar 

  55. Forini F, Paolicchi A, Pizzorusso T, Ratto GM, Saviozzi M, Vanini V, et al. 3,5,3′-Triiodothyronine deprivation affects phenotype and intracellular [Ca2+]i of human cardiomyocytes in culture. Cardiovasc Res. 2001;51(2):322–30.

    Article  CAS  Google Scholar 

  56. Schwarz K, Siddiqi N, Singh S, Neil CJ, Dawson DK, Frenneaux MP. The breathing heart. Mitochondrial respiratory chain dysfunction in cardiac disease. Int J Cardiol. 2014;171(2:134–43. https://doi.org/10.1016/j.ijcard.2013.12.014.

    Article  Google Scholar 

  57. Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, et al. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res. 2001;88:529–35. https://doi.org/10.1161/01.RES.88.5.529.

    Article  PubMed  CAS  Google Scholar 

  58. Tavares AM, da Rosa Araujo AS, Llesuy S, Khaper N, Rohde LE, Clausell N, et al. Early loss of cardiac function in acute myocardial infarction is associated with redox imbalance. Exp Clin Cardiol. 2012;17:263–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  59. Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1α. Cardiovasc Res. 2008;79(2):208–17. https://doi.org/10.1093/cvr/cvn098.

    Article  PubMed  CAS  Google Scholar 

  60. McLeod CJ, Pagel I, Sack MN. The mitochondrial biogenesis regulatory program adaptation to ischemia—a putative target for therapeutic intervention. Trends Cardiovasc Med. 2005;15:118–23. https://doi.org/10.1016/j.tcm.2005.05.001.

    Article  PubMed  CAS  Google Scholar 

  61. Hock MB, Kralli A. Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol. 2009;71:177–03. https://doi.org/10.1146/annurev.physiol.010908.163119.

    Article  PubMed  CAS  Google Scholar 

  62. Kunkel GH, Chaturvedi P, Tyagi SC. Mitochondrial pathways to cardiac recovery: TFAM. Heart Fail Rev. 2016;21(5):499–517. https://doi.org/10.1007/s10741-016-9561-8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Karamanlidis G, Nascimben L, Couper GS, Shekar PS, del Monte F, Tian R. Defective DNA replication impairs mitochondrial biogenesis in human failing hearts: mitochondrial biogenesis in human heart failure. Circ Res. 2010;106(9):1541–8. https://doi.org/10.1161/CIRCRESAHA.109.212753.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Sihag S, Li AY, Cresci S, Sucharov CC, Lehman JJ. PGC-1α and ERRα target gene down-regulation is a signature of the failing human heart. J Mol Cell Cardiol. 2009;46(2):201–12. https://doi.org/10.1016/j.yjmcc.2008.10.025.

    Article  PubMed  CAS  Google Scholar 

  65. Arany Z, Novikov M, Chin S, Ma Y, Rosenzweig A, Spiegelman BM. Transverse aortic constriction leads to accelerated heart failure in mice lacking PPARγ coactivator 1α. Proc Natl Acad Sci U S A. 2006;103:10086–91. https://doi.org/10.1073/pnas.0603615103.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Garnier A, Fortin D, Deloménie C, Momken I, Veksler V, Ventura-Clapier R. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol. 2003;551:491–501. https://doi.org/10.1113/jphysiol.2003.045104.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Ahuja P, Angelis E, Ruan H, Korge P, Olson A, et al. Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice. J Clin Investig. 2010;120:1494–505. https://doi.org/10.1172/JCI38331.

    Article  PubMed  CAS  Google Scholar 

  68. Yan W, Zhang H, Liu P, Wang H, Liu J, Gao C, et al. Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1α signaling contributing to increased vulnerability in diabetic heart. Basic Res Cardiol. 2013;108(3):329. https://doi.org/10.1007/s00395-013-0329-1.

    Article  PubMed  CAS  Google Scholar 

  69. Sun L, Zhao M, Yu XJ, Wang H, He X, Liu JK, et al. Cardioprotection by acetylcholine: a novel mechanism via mitochondrial biogenesis and function involving the PGC-1α pathway. J Cell Physiol. 2013;228:1238–48. https://doi.org/10.1002/jcp.24277.

    Article  PubMed  CAS  Google Scholar 

  70. Butterick TA, Hocum SL, Duffy C, Holley C, Cabrera JA, Crampton M, et al. Pioglitazone increases PGC1-α signaling within chronically ischemic myocardium. Basic Res Cardiol. 2016;111(3):37. https://doi.org/10.1007/s00395-016-0555-4.

    Article  PubMed  Google Scholar 

  71. Ikeuchi M, Matsusaka H, Kang D, Matsushima S, Ide T, Kubota T, et al. Overexpression of mitochondrial transcription factor a ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction. Circulation. 2005;112(5):683–90. https://doi.org/10.1161/CIRCULATIONAHA.104.524835.

    Article  PubMed  CAS  Google Scholar 

  72. Weitzel JM, Iwen KA. Coordination of mitochondrial biogenesis by thyroid hormone. Mol Cell Endocrinol. 2011;342(1–2):1–7. https://doi.org/10.1016/j.mce.2011.05.009.

    Article  PubMed  CAS  Google Scholar 

  73. Wulf A, Harneit A, Kröger M, Kebenko M, Wetzel MG, Weitzel JM. T3-mediated expression of PGC-1α via a far upstream located thyroid hormone response element. Mol Cell Endocrinol. 2008;287:90–5. https://doi.org/10.1016/j.mce.2008.01.017.

    Article  PubMed  CAS  Google Scholar 

  74. Paradies G, Paradies V, De Benedictis V, Ruggiero FM, Petrosillo G. Functional role of cardiolipin in mitochondrial bioenergetics. Biochim Biophys Acta. 2014;1837(4):408–17. https://doi.org/10.1016/j.bbabio.2013.10.006.

    Article  PubMed  CAS  Google Scholar 

  75. Pfeiffer K, Gohil V, Stuart RA, Hunte C, Brandt U, Greenberg ML, et al. Cardiolipin stabilizes respiratory chain supercomplexes. J Biol Chem. 2003;278(52):52873–80. https://doi.org/10.1074/jbc.M308366200.

    Article  PubMed  CAS  Google Scholar 

  76. Zhang M, Mileykovskaya E, Dowhan W. Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane. J Biol Chem. 2002;277(46):43553–6. https://doi.org/10.1074/jbc.C200551200.

    Article  PubMed  CAS  Google Scholar 

  77. Chicco AJ, Sparagna GC. Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol. 2007;292:C33–44. https://doi.org/10.1152/ajpcell.00243.2006.

    Article  PubMed  CAS  Google Scholar 

  78. Paradies G, Paradies V, Ruggiero FM, Petrosillo G. Mitochondrial bioenergetics and cardiolipin alterations in myocardial ischemia/reperfusion injury. Implications for pharmacological cardioprotection. Am J Physiol Heart Circ Physiol. 2018;315:H1341–52. https://doi.org/10.1152/ajpheart.00028.2018.

    Article  PubMed  CAS  Google Scholar 

  79. Cao SG, Cheng P, Angel A, Hatch GM. Thyroxine stimulates phosphatidylglycerolphosphate synthase activity in rat heart mitochondria. Biochim Biophys Acta. 1995;1256(2):241–4. https://doi.org/10.1016/0005-2760(95)00035-B.

    Article  PubMed  Google Scholar 

  80. Mutter T, Dolinsky VW, Ma BJ, Taylor WA, Hatch GM. Thyroxine regulation of monolysocardiolipin acyltransferase activity in rat heart. Biochem J. 2000;346(2):403–6.

    Article  CAS  Google Scholar 

  81. Paradies G, Ruggiero FM, Petrosillo G, Quagliariello E. Enhanced cytochrome oxidase activity and modification of lipids in heart mitochondria from hyperthyroid rats. Biochim Biophys Acta. 1994;1225(2):165–70.

    Article  CAS  Google Scholar 

  82. Paradies G, Ruggiero FM, Dinoi P, Petrosillo G, Quagliariello E. Decreased cytochrome oxidase activity and changes in phospholipids in heart mitochondria from hypothyroid rats. Arch Biochem Biophys. 1993;307(1):91–5.

    Article  CAS  Google Scholar 

  83. Gottlieb RA, Bernstein D. Mitochondrial remodeling: rearranging, recycling, and reprogramming. Cell Calcium. 2016;60(2):88–101. https://doi.org/10.1016/j.ceca.2016.04.006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Shirihai OS, Song M, Dorn GW. How mitochondrial dynamism orchestrates mitophagy. Circ Res. 2015;116(11):1835–49. https://doi.org/10.1161/CIRCRESAHA.116.306374.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Dorn GW, Kitsis RN. The mitochondrial dynamism-mitophagy-cell death interactome: multiple roles performed by members of a mitochondrial molecular ensemble. Circ Res. 2015;116(1):167–82. https://doi.org/10.1161/CIRCRESAHA.116.303554.

    Article  PubMed  CAS  Google Scholar 

  86. Dhingra R, Kirshenbaum LA. Regulation of mitochondrial dynamics and cell fate. Circ J. 2014;78(4):803–10.

    Article  CAS  Google Scholar 

  87. Thomas RL, Gustafsson AB. Mitochondrial autophagy—an essential quality control mechanism for myocardial homeostasis. Circ J. 2013;77:2449–54.

    Article  CAS  Google Scholar 

  88. Okamoto K, Shaw JM. Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. Annu Rev Genet. 2005;39:503–36. https://doi.org/10.1146/annurev.genet.38.072902.093019.

    Article  PubMed  CAS  Google Scholar 

  89. Song Z, Ghochani M, McCaffery JM, Frey TG, Chan DC. Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. Mol Biol Cell. 2009;20(15):3525–32. https://doi.org/10.1091/mbc.E09-03-025.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Yoon Y, Krueger EW, Oswald BJ, McNiven MA. The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol. 2003;23(15):5409–20. https://doi.org/10.1128/MCB.23.15.5409-5420.200.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Kanzaki Y, Terasaki F, Okabe M, Otsuka K, Katashima T, Fujita S, et al. Giant mitochondria in the myocardium of a patient with mitochondrial cardiomyopathy: transmission and 3-dimensional scanning electron microscopy. Circulation. 2010;121:831–2. https://doi.org/10.1161/CIR.0b013e3181d22e2d.

    Article  PubMed  Google Scholar 

  92. Pennanen C, Parra V, López-Crisosto C, Morales PE, Del Campo A, Gutierrez T, et al. Mitochondrial fission is required for cardiomyocyte hypertrophy mediated by a Ca2+-calcineurin signaling pathway. J Cell Sci. 2014;127(12):2659–71. https://doi.org/10.1242/jcs.139394.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Zhou H, Hu S, Jin Q, Shi C, Zhang Y, Zhu P, et al. Mff-dependent mitochondrial fission contributes to the pathogenesis of cardiac microvasculature ischemia/reperfusion injury via induction of mROS-mediated cardiolipin oxidation and HK2/VDAC1 disassociation-involved mPTP opening. J Am Heart Assoc. 2017;6(3):e005328. https://doi.org/10.1161/JAHA.116.005328.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Yu T, Sheu SS, Robotham JL, Yoon Y. Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res. 2008;79(2):341–51. https://doi.org/10.1093/cvr/cvn104.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Ong SB, Subrayan S, Lim SY, Yellon DM, Davidson SM, Hausenloy DJ. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010;121(8):2012–22. https://doi.org/10.1161/CIRCULATIONAHA.109.906610.

    Article  PubMed  CAS  Google Scholar 

  96. Sharp W, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, et al. Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J. 2014;28(1):316–26. https://doi.org/10.1096/fj.12-226225.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Fang L, Moore XL, Gao XM, Dart AM, Lim YL, Du XJ. Down-regulation of mitofusin-2 expression in cardiac hypertrophy in vitro and in vivo. Life Sci. 2007;80(23):2154–60. https://doi.org/10.1016/j.lfs.2007.04.003.

    Article  PubMed  CAS  Google Scholar 

  98. Yu H, Guo Y, Mi L, Wang X, Li L, Gao W. Mitofusin 2 inhibits angiotensin II-induced myocardial hypertrophy. J Cardiovasc Pharmacol Ther. 2011;16(2):205–11. https://doi.org/10.1177/1074248410385683.

    Article  PubMed  CAS  Google Scholar 

  99. Zhao T, Huang X, Han L, Wang X, Cheng H, Zhao Y, et al. Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes. J Biol Chem. 2012;287(28):23615–25. https://doi.org/10.1074/jbc.M112.379164.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Chen Y, Dorn GW II. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science. 2013;340(6131):471–5. https://doi.org/10.1126/science.1231031.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Campos JC, Bozi LH, Bechara LR, Lima VM, Ferreira JC. Mitochondrial quality control in cardiac diseases. Front Physiol. 2016;7:479. https://doi.org/10.3389/fphys.2016.00479.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Zhang W, Chen C, Wang J, Liu L, He Y, Chen Q. Mitophagy in cardiomyocytes and in platelets: a major mechanism of cardioprotection against ischemia/reperfusion injury. Physiology. 2018;33(2):86–98. https://doi.org/10.1152/physiol.00030.2017.

    Article  PubMed  CAS  Google Scholar 

  103. Sinha RA, Singh BK, Zhou J, Wu Y, Farah BL, Ohba K, et al. Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling. Autophagy. 2015;11(8):1341–57. https://doi.org/10.1080/15548627.2015.1061849.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Singh BK, Sinha RA, Tripathi M, Mendoza A, Ohba K, Sy JAC, et al. Thyroid hormone receptor and ERRα coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function. Sci Signal. 2018;11(536):eaam5855. https://doi.org/10.1126/scisignal.aam5855.

    Article  PubMed  CAS  Google Scholar 

  105. Lesmana R, Sinha RA, Singh BK, Zhou J, Ohba K, Wu Y, et al. Thyroid hormone stimulation of autophagy is essential for mitochondrial biogenesis and activity in skeletal muscle. Endocrinology. 2016;157(1):23–38. https://doi.org/10.1210/en.2015-1632.

    Article  PubMed  CAS  Google Scholar 

  106. Bhujabal Z. FKBP8 recruits LC3A to mediate Parkin-independent mitophagy. EMBO Rep. 2017;18(6):947–61. https://doi.org/10.15252/embr.201643147.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. De Castro AL, Tavares AV, Campos C, Fernandes RO, Siqueira R, Conzatti A, et al. Cardioprotective effects of thyroid hormones in a rat model of myocardial infarction are associated with oxidative stress reduction. Mol Cell Endocrinol. 2014;391(1–2):22–9. https://doi.org/10.1016/j.mce.2014.04.010.

    Article  PubMed  CAS  Google Scholar 

  108. De Castro AL, Tavares AV, Fernandes RO, Campos C, Conzatti A, Siqueira R, et al. T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats. Mol Cell Biochem. 2015;408(1–2):235–43. https://doi.org/10.1007/s11010-015-2501-4.

    Article  PubMed  CAS  Google Scholar 

  109. Corssac G, de Castro AL, Tavares AV, Campos C, Fernandes RO, Ortiz VD, et al. Thyroid hormones effects on oxidative stress and cardiac remodeling in the right ventricle of infarcted rats. Life Sci. 2016;146(1):109–16. https://doi.org/10.1016/j.lfs.2015.12.052.

    Article  PubMed  CAS  Google Scholar 

  110. Li Q, Qi X, Jia W. 3,3′,5-triiodothyroxine inhibits apoptosis and oxidative stress by the PKM2/PKM1 ratio during oxygen-glucose deprivation/reperfusion AC16 and HCM-a cells: T3 inhibits apoptosis and oxidative stress by PKM2/PKM1 ratio. Biochem Biophys Res Commun. 2016;475(1):51–6. https://doi.org/10.1016/j.bbrc.2016.05.030.

    Article  PubMed  CAS  Google Scholar 

  111. Xu M, Yigang W, Ahmar A, Muhammad A. Mitochondrial KATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential. Am J Physiol Heart Circ Physiol. 2001;281:H1295–303.

    Article  CAS  Google Scholar 

  112. Galluzzi L, Kepp O, Kroemer G. Mitochondria: master regulators of danger signaling. Nat Rev Mol Cell Biol. 2012;13:780–8. https://doi.org/10.1038/nrm3479.

    Article  PubMed  CAS  Google Scholar 

  113. Whelan RS, Kaplinskiy V, Kitsis RN. Cell death in the pathogenesis of heart disease mechanisms and significance. Annu Rev Physiol. 2010;72:19–44. https://doi.org/10.1146/annurev.physiol.010908.163111.

    Article  CAS  Google Scholar 

  114. Ren J, Zhang S, Kovacs A, Wang Y, Muslin AJ. Role of p38α MAPK in cardiac apoptosis and remodeling after myocardial infarction. J Mol Cell Cardiol. 2005;38(4):617–23. https://doi.org/10.1016/j.yjmcc.2005.01.012.

    Article  PubMed  CAS  Google Scholar 

  115. Capano M, Crompton M. Bax translocates to mitochondria of heart cells during simulated ischaemia: involvement of AMP-activated and p38 mitogen-activated protein kinases. Biochem J. 2006;395:57–64. https://doi.org/10.1042/BJ20051654.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Kaiser RA, Bueno OF, Lips DJ, Doevendans PA, Jones F, Kimball TF, et al. Targeted inhibition of p38 mitogen-activated protein kinase antagonizes cardiac injury and cell death following ischemia-reperfusion in vivo. J Biol Chem. 2004;279(15):15524–30. https://doi.org/10.1074/jbc.M313717200.

    Article  PubMed  CAS  Google Scholar 

  117. Jeong CW, Yoo KY, Lee SH, Jeong HJ, Lee CS, Kim SJ. Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK. J Cardiovasc Pharmacol Ther. 2012;17(4):387–94. https://doi.org/10.1177/1074248412438102.

    Article  PubMed  CAS  Google Scholar 

  118. Ma XL, Kumar S, Gao F, Louden CS, Lopez BL, Christopher TA, et al. Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation. 1999;99:1685–9. https://doi.org/10.1161/01.CIR.99.13.1685.

    Article  PubMed  CAS  Google Scholar 

  119. Kennedy SG, et al. Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol Cell Biol. 1999;19(8):5800–10.

    Article  CAS  Google Scholar 

  120. Ong SB, Hall AR, Dongworth RK, Kalkhoran S, Pyakurel A, Scorrano L, et al. Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology. Thromb Haemost. 2015;113(3):513–21. https://doi.org/10.1160/TH14-07-0592.

    Article  PubMed  Google Scholar 

  121. Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012;149(7):1536–48. https://doi.org/10.1016/j.cell.2012.05.014.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Wang JX, Jiao JQ, Li Q, Long B, Wang K, Liu JP, et al. miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat Med. 2011;17(1):71–8. https://doi.org/10.1038/nm.2282.

    Article  PubMed  CAS  Google Scholar 

  123. Guo X, Sesaki H, Qi X. Drp1 stabilizes p53 on the mitochondria to trigger necrosis under oxidative stress conditions in vitro and in vivo. Biochem J. 2014;461(1):137–46. https://doi.org/10.1042/BJ20131438.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Genovese T, Impellizzeri D, Ahmad A, Cornelius C, Campolo M, Cuzzocrea S, et al. Post ischaemic thyroid hormone treatment in a rat model of acute stroke. Brain Res. 2013;1513:92–102. https://doi.org/10.1016/j.brainres.2013.03.001.

    Article  PubMed  CAS  Google Scholar 

  125. Pantos CI, Malliopoulou VA, Mourouzis IS, Karamanoli EP, Tzeis SM, Carageorgiou HC, et al. Long-term thyroxine administration increases HSP70 mRNA expression and attenuates p38 MAP kinase activity in response to ischaemia. J Endocrinol. 2001;170(1):207–15. https://doi.org/10.1677/joe.0.1700207.

    Article  PubMed  CAS  Google Scholar 

  126. Pantos C, Mourouzis I, Saranteas T, Clavé G, Ligeret H, Noack-Fraissignes P, et al. Thyroid hormone improves postischaemic recovery of function while limiting apoptosis: a new therapeutic approach to support hemodynamics in the setting of ischaemia-reperfusion? Basic Res Cardiol. 2009;104(1):69–77. https://doi.org/10.1007/s00395-008-0758.

    Article  PubMed  CAS  Google Scholar 

  127. Mourouzis I, Kostakou E, Galanopoulos G, Mantzouratou P, Pantos C. Inhibition of thyroid hormone receptor α1 impairs post ischemic cardiac performance after myocardial infarction in mice. Mol Cell Biochem. 2013;379(1–2):97–105. https://doi.org/10.1007/s11010-013-1631-9.

    Article  PubMed  CAS  Google Scholar 

  128. Kuzman JA, Gerdes AM, Kobayashi S, Liang Q. Thyroid hormone activates Akt and prevents serum starvation-induced cell death in neonatal rat cardiomyocytes. J Mol Cell Cardiol. 2005;39(5):841–4. https://doi.org/10.1016/j.yjmcc.2005.07.019.

    Article  PubMed  CAS  Google Scholar 

  129. Mourouzis I, Mantzouratou P, Galanopoulos G, Kostakou E, Roukounakis N, Kokkinos AD, et al. Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings. Mol Cell Biochem. 2012;363(1–2):235–43. https://doi.org/10.1007/s11010-011-1175-9.

    Article  PubMed  CAS  Google Scholar 

  130. Nicolini G, Forini F, Kusmic C, Pitto L, Mariani L, Iervasi G. Early and short-term triiodothyronine supplementation prevents adverse post-ischemic cardiac remodeling: role of transforming growth factor-β1 and anti-fibrotic miRNA signaling. Mol Med. 2016;21(1):900–11. https://doi.org/10.2119/molmed.2015.00140.

    Article  PubMed  CAS  Google Scholar 

  131. Mak TW, Hauck L, Grothe D, Billia F. p53 regulates the cardiac transcriptome. Proc Natl Acad Sci U S A. 2017;114(9):2331–6. https://doi.org/10.1073/pnas.1621436114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Piek A, de Boer RA, Silljé HH. The fibrosis-cell death axis in heart failure. Heart Fail Rev. 2016;21(2):199–211. https://doi.org/10.1007/s10741-016-9536-9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  133. Chiong M, Wang ZV, Pedrozo Z, Cao DJ, Troncoso R, Ibacache M, et al. Cardiomyocyte death: mechanisms and translational implications. Cell Death Dis. 2011;2:e244. https://doi.org/10.1038/cddis.2011.130.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425(6958):577–84.

    Article  CAS  Google Scholar 

  135. van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science. 2007;316(5824):575–9. https://doi.org/10.1126/science.1139089.

    Article  PubMed  CAS  Google Scholar 

  136. Barringhaus KG, Zamore PD. MicroRNAs: regulating a change of heart. Circulation. 2009;119(16):2217–24. https://doi.org/10.1161/CIRCULATIONAHA.107.715839.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Divakaran V, Mann DL. The emerging role of microRNAs in cardiac remodeling and heart failure. Circ Res. 2008;103(10):1072–83. https://doi.org/10.1161/CIRCRESAHA.108.183087.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Thum T, et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007;116(3):258–67. https://doi.org/10.1161/CIRCULATIONAHA.107.687947.

    Article  PubMed  CAS  Google Scholar 

  139. van Rooij E, Marshall W, Olson E. Toward MicroRNA-based therapeutics for heart disease: the sense in antisense. Circ Res. 2008;103(9):919–28. https://doi.org/10.1161/CIRCRESAHA.108.183426.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Zhang X, Wang X, Zhu H, Zhu C, Wang Y, Pu WT, et al. Synergistic effects of the GATA-4-mediated miR-144/451 cluster in protection against simulated ischemia/reperfusion-induced cardio myocyte death. J Mol Cell Cardiol. 2010;49(5):841–50. https://doi.org/10.1016/j.yjmcc.2010.08.007.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Li J, Donath S, Li Y, Qin D, Prabhakar BS, Li P. miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway. PLoS Genet. 2010;6(1):e1000795. https://doi.org/10.1371/journal.pgen.1000795.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Li S, Xiao FY, Shan PR, Su L, Chen DL, Ding JY, et al. Overexpression of microRNA-133a inhibits ischemia-reperfusion-induced cardiomyocyte apoptosis by targeting DAPK2. J Hum Genet. 2015;60(11):709–16. https://doi.org/10.1038/jhg.2015.96.

    Article  PubMed  CAS  Google Scholar 

  143. Janssen R, Zuidwijk MJ, Kuster DW, Muller A, Simonides WS. Thyroid hormone-regulated cardiac microRNAs are predicted to suppress pathological hypertrophic signaling. Front Endocrinol (Lausanne). 2014;5:171. https://doi.org/10.3389/fendo.2014.00171. eCollection 2014.

    Article  Google Scholar 

  144. Janssen R, Zuidwijk MJ, Muller A, van Mil A, Dirkx E, Oudejans CB, et al. MicroRNA 214 is a potential regulator of thyroid hormone levels in the mouse heart following myocardial infarction, by targeting the thyroid-hormone-inactivating enzyme deiodinase type III. Front Endocrinol (Lausanne). 2016;7:22. https://doi.org/10.3389/fendo.2016.00022. eCollection 2016.

    Article  Google Scholar 

  145. Wang Y, Men M, Yang W, Zheng H, Xue S. MiR-31 downregulation protects against cardiac ischemia/reperfusion injury by targeting protein kinase C epsilon (PKCε) directly. Cell Physiol Biochem. 2015;36:179–90. https://doi.org/10.1159/000374062.

    Article  PubMed  CAS  Google Scholar 

  146. Martinez EC, Lilyanna S, Wang P, Vardy LA, Jiang X, Armugam A, et al. MicroRNA-31 promotes adverse cardiac remodeling and dysfunction in ischemic heart disease. J Mol Cell Cardiol. 2017;112:27–39. https://doi.org/10.1016/j.yjmcc.2017.08.013.

    Article  PubMed  CAS  Google Scholar 

  147. Su M, Chen Z, Wang C, Song L, Zou Y, Zhang L, et al. Cardiac-specific overexpression of miR-222 induces heart failure and inhibits autophagy in mice. Cell Physiol Biochem. 2016;39(4):1503–11. https://doi.org/10.1159/000447853.

    Article  PubMed  CAS  Google Scholar 

  148. Seok HY, Chen J, Kataoka M, Huang ZP, Ding J, Yan J, et al. Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy. Circ Res. 2014;114(10):1585–95. https://doi.org/10.1161/CIRCRESAHA.114.303784.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francesca Forini .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Forini, F., Pitto, L., Nicolini, G. (2020). Thyroid Hormone, Mitochondrial Function and Cardioprotection. In: Iervasi, G., Pingitore, A., Gerdes, A., Razvi, S. (eds) Thyroid and Heart . Springer, Cham. https://doi.org/10.1007/978-3-030-36871-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-36871-5_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-36870-8

  • Online ISBN: 978-3-030-36871-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics