Skip to main content
SpringerLink
Log in

The Role of Redox Signalling in Cardiovascular Regeneration

  • Chapter
  • First Online:
Oxidative Stress in Heart Diseases

Abstract

Cardiovascular disease (CVD) is a major public health problem, particularly in the industrialised world, with diverse causes. Central to these underlying aetiologies is a progressive loss of functional cardiomyocytes, maladaptive remodelling, and resultant cardiac dysfunction. The ageing heart is characterised by perturbations in numerous signalling pathways, impairing its ability to repair and replace injured cardiomyocytes. This is caused at least in part by dysregulation of redox signalling- both in regard to production of reactive oxygen species (ROS), and disruption of cellular protective mechanisms. Cardiac regeneration is one area of particular therapeutic promise, which seeks to ameliorate cardiac function by either (1) direct application of stem cells, (2) modification of molecular signalling pathways to restore the endogenous reparative capacity of the heart, or (3) a combination of these two approaches. Unravelling these molecular and cellular signalling pathways is paramount to unlocking the potential of cardiac regenerative therapies, and theoretically revolutionising the medical management of patients with heart failure.

In this chapter, we will review the role of oxidative stress in cardiovascular disease, and the pathophysiological molecular signalling pathways that are involved in the transition from young to ageing heart. We will then provide an overview of the molecular therapies that are used to target these pathways to enhance heart regeneration, future directions involving cellular and novel ‘bio-printing’ based approaches, in addition to current promising clinical trials.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
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. Aonuma T, Takehara N, Maruyama K, Kabara M, Matsuki M, Yamauchi A, Kawabe J, Hasebe N (2016) Apoptosis-resistant cardiac progenitor cells modified with apurinic/apyrimidinic endonuclease/redox factor 1 gene overexpression regulate cardiac repair after myocardial infarction. Stem Cells Transl Med 5:1067–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Arabacilar P, Marber M (2015) The case for inhibiting p38 mitogen-activated protein kinase in heart failure. Front Pharmacol 6:102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisen J (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bolli R, Chugh AR, D’Amario D, Loughran JH, Stoddard MF, Ikram S, Beache GM, Wagner SG, Leri A, Hosoda T, Sanada F, Elmore JB, Goichberg P, Cappetta D, Solankhi NK, Fahsah I, Rokosh DG, Slaughter MS, Kajstura J, Anversa P (2011) Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 378:1847–1857

    Article  PubMed  PubMed Central  Google Scholar 

  5. Briceno N, Schuster A, Lumley M, Perera D (2016) Ischaemic cardiomyopathy: pathophysiology, assessment and the role of revascularisation. Heart 102:397–406

    Article  CAS  PubMed  Google Scholar 

  6. Brugts JJ, van Vark L, Akkerhuis M, Bertrand M, Fox K, Mourad JJ, Boersma E (2015) Impact of renin-angiotensin system inhibitors on mortality and major cardiovascular endpoints in hypertension: a number-needed-to-treat analysis. Int J Cardiol 181:425–429

    Article  PubMed  Google Scholar 

  7. Bubb KJ, Birgisdottir AB, Tang O, Hansen T, Figtree GA (2017) Redox modification of caveolar proteins in the cardiovascular system- role in cellular signalling and disease. Free Radic Biol Med 109:61–74

    Article  CAS  PubMed  Google Scholar 

  8. Cabrera-Fuentes HA, Aragones J, Bernhagen J, Boening A, Boisvert WA, Botker HE, Bulluck H, Cook S, Di Lisa F, Engel FB, Engelmann B, Ferrazzi F, Ferdinandy P, Fong A, Fleming I, Gnaiger E, Hernandez-Resendiz S, Kalkhoran SB, Kim MH, Lecour S, Liehn EA, Marber MS, Mayr M, Miura T, Ong SB, Peter K, Sedding D, Singh MK, Suleiman MS, Schnittler HJ, Schulz R, Shim W, Tello D, Vogel CW, Walker M, Li QO, Yellon DM, Hausenloy DJ, Preissner KT (2016) From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”. Basic Res Cardiol 111:69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cambria E, Pasqualini FS, Wolint P, Gunter J, Steiger J, Bopp A, Hoerstrup SP, Emmert MY (2017) Translational cardiac stem cell therapy: advancing from first-generation to next-generation cell types. NPJ Regen Med 2:17

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cannata A, Camparini L, Sinagra G, Giacca M, Loffredo FS (2016) Pathways for salvage and protection of the heart under stress: novel routes for cardiac rejuvenation. Cardiovasc Res 111:142–153

    Article  CAS  PubMed  Google Scholar 

  11. Cesselli D, Aleksova A, Sponga S, Cervellin C, Di Loreto C, Tell G, Beltrami AP (2017) Cardiac cell senescence and redox signaling. Front Cardiovasc Med 4:38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen CA, Wang TY, Varadharaj S, Reyes LA, Hemann C, Talukder MA, Chen YR, Druhan LJ, Zweier JL (2010) S-glutathionylation uncouples eNOS and regulates its cellular and vascular function. Nature 468:1115–1118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen J, Song W, Amato K (2015) Eph receptor tyrosine kinases in cancer stem cells. Cytokine Growth Factor Rev 26:1–6

    Article  CAS  PubMed  Google Scholar 

  14. Cheng G, Wei L, Xiurong W, Xiangzhen L, Shiguang Z, Songbin F (2009) IL-17 stimulates migration of carotid artery vascular smooth muscle cells in an MMP-9 dependent manner via p38 MAPK and ERK1/2-dependent NF-kappaB and AP-1 activation. Cell Mol Neurobiol 29:1161–1168

    Article  CAS  PubMed  Google Scholar 

  15. Collins LR, Priest C, Caras I, Littman N, Kadyk L (2015) Proceedings: moving toward cell-based therapies for heart disease. Stem Cells Transl Med 4:863–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Contreras A, Orozco AF, Resende M, Schutt RC, Traverse JH, Henry TD, Lai D, Cooke JP, Bolli R, Cohen ML, Moye L, Pepine CJ, Yang PC, Perin EC, Willerson JT, Taylor DA, Cardiovascular Cell Therapy Research N (2017) Identification of cardiovascular risk factors associated with bone marrow cell subsets in patients with STEMI: a biorepository evaluation from the CCTRN TIME and LateTIME clinical trials. Basic Res Cardiol 112:3

    Article  CAS  PubMed  Google Scholar 

  17. Csiszar A, Labinskyy N, Perez V, Recchia FA, Podlutsky A, Mukhopadhyay P, Losonczy G, Pacher P, Austad SN, Bartke A, Ungvari Z (2008) Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol 295:H1882–H1894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Di Baldassarre A, Cimetta E, Bollini S, Gaggi G, Ghinassi B (2018) Human-induced pluripotent stem cell technology and cardiomyocyte generation: progress and clinical applications. Cells 7

    Google Scholar 

  19. Dumitrascu R, Kulcke C, Konigshoff M, Kouri F, Yang X, Morrell N, Ghofrani HA, Weissmann N, Reiter R, Seeger W, Grimminger F, Eickelberg O, Schermuly RT, Pullamsetti SS (2011) Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats. Eur Respir J 37:1104–1118

    Article  CAS  PubMed  Google Scholar 

  20. Ellison GM, Torella D, Dellegrottaglie S, Perez-Martinez C, Perez de Prado A, Vicinanza C, Purushothaman S, Galuppo V, Iaconetti C, Waring CD, Smith A, Torella M, Cuellas Ramon C, Gonzalo-Orden JM, Agosti V, Indolfi C, Galinanes M, Fernandez-Vazquez F, Nadal-Ginard B (2011) Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart. J Am Coll Cardiol 58:977–986

    Article  CAS  PubMed  Google Scholar 

  21. Engel FB, Hsieh PC, Lee RT, Keating MT (2006) FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction. Proc Natl Acad Sci U S A 103:15546–15551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gentile C (2016) Filling the gaps between the in vivo and in vitro microenvironment: engineering of spheroids for stem cell technology. Curr Stem Cell Res Ther 11:652–665

    Article  CAS  PubMed  Google Scholar 

  23. Goichberg P, Kannappan R, Cimini M, Bai Y, Sanada F, Sorrentino A, Signore S, Kajstura J, Rota M, Anversa P, Leri A (2013) Age-associated defects in EphA2 signaling impair the migration of human cardiac progenitor cells. Circulation 128:2211–2223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Goichberg P, Chang J, Liao R, Leri A (2014) Cardiac stem cells: biology and clinical applications. Antioxid Redox Signal 21:2002–2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Guo J, Jie W, Shen Z, Li M, Lan Y, Kong Y, Guo S, Li T, Zheng S (2014) SCF increases cardiac stem cell migration through PI3K/AKT and MMP2/9 signaling. Int J Mol Med 34:112–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hafstad AD, Nabeebaccus AA, Shah AM (2013) Novel aspects of ROS signalling in heart failure. Basic Res Cardiol 108:359

    Article  CAS  PubMed  Google Scholar 

  27. Hao J, Du H, Li W, Liu F, Lu J, Yang X, Cui W (2016) Anthocyanins protected hearts against ischemic injury by reducing MMP-2 activity via Akt/P38 pathways. Am J Transl Res 8:1100–1107

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Herrero D, Tome M, Canon S, Cruz FM, Carmona RM, Fuster E, Roche E, Bernad A (2018) Redox-dependent BMI1 activity drives in vivo adult cardiac progenitor cell differentiation. Cell Death Differ 25:807–820

    Article  CAS  PubMed Central  Google Scholar 

  29. Heusch G (2015) Mitochondria at the heart of cardiovascular protection: p66shc-friend or foe? Eur Heart J 36:469–471

    Article  PubMed  Google Scholar 

  30. Hong KU, Guo Y, Li QH, Cao P, Al-Maqtari T, Vajravelu BN, Du J, Book MJ, Zhu X, Nong Y, Bhatnagar A, Bolli R (2014) c-kit+ Cardiac stem cells alleviate post-myocardial infarction left ventricular dysfunction despite poor engraftment and negligible retention in the recipient heart. PLoS One 9:e96725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hou J, Wang L, Long H, Wu H, Wu Q, Zhong T, Chen X, Zhou C, Guo T, Wang T (2017) Hypoxia preconditioning promotes cardiac stem cell survival and cardiogenic differentiation in vitro involving activation of the HIF-1alpha/apelin/APJ axis. Stem Cell Res Ther 8:215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ito K, Suda T (2014) Metabolic requirements for the maintenance of self-renewing stem cells. Nat Rev Mol Cell Biol 15:243–256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jung SN, Yang WK, Kim J, Kim HS, Kim EJ, Yun H, Park H, Kim SS, Choe W, Kang I, Ha J (2008) Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells. Carcinogenesis 29:713–721

    Article  CAS  PubMed  Google Scholar 

  34. Katz JN, Waters SB, Hollis IB, Chang PP (2015) Advanced therapies for end-stage heart failure. Curr Cardiol Rev 11:63–72

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kelley MR, Georgiadis MM, Fishel ML (2012) APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1. Curr Mol Pharmacol 5:36–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kittleson MM (2018) Recent advances in heart transplantation. F1000Res:7

    Google Scholar 

  37. Kocabas F, Mahmoud AI, Sosic D, Porrello ER, Chen R, Garcia JA, DeBerardinis RJ, Sadek HA (2012) The hypoxic epicardial and subepicardial microenvironment. J Cardiovasc Transl Res 5:654–665

    Article  PubMed  Google Scholar 

  38. Kohler AC, Sag CM, Maier LS (2014) Reactive oxygen species and excitation-contraction coupling in the context of cardiac pathology. J Mol Cell Cardiol 73:92–102

    Article  CAS  PubMed  Google Scholar 

  39. Larson MG (1995) Assessment of cardiovascular risk factors in the elderly: the Framingham Heart Study. Stat Med 14:1745–1756

    Article  CAS  PubMed  Google Scholar 

  40. Leong YY, Ng WH, Ellison-Hughes GM, Tan JJ (2017) Cardiac stem cells for myocardial regeneration: they are not alone. Front Cardiovasc Med 4:47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lin Z, Pu WT (2014) Strategies for cardiac regeneration and repair. Sci Transl Med 6:239rv231

    Article  CAS  Google Scholar 

  42. Lundy SD, Gantz JA, Pagan CM, Filice D, Laflamme MA (2014) Pluripotent stem cell derived cardiomyocytes for cardiac repair. Curr Treat Options Cardiovasc Med 16:319

    Article  PubMed  PubMed Central  Google Scholar 

  43. Luo YX, Tang X, An XZ, Xie XM, Chen XF, Zhao X, Hao DL, Chen HZ, Liu DP (2017) SIRT4 accelerates Ang II-induced pathological cardiac hypertrophy by inhibiting manganese superoxide dismutase activity. Eur Heart J 38:1389–1398

    Article  CAS  PubMed  Google Scholar 

  44. Mandal CC, Ganapathy S, Gorin Y, Mahadev K, Block K, Abboud HE, Harris SE, Ghosh-Choudhury G, Ghosh-Choudhury N (2011) Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation. Biochem J 433:393–402

    Article  CAS  PubMed  Google Scholar 

  45. Mao AS, Mooney DJ (2015) Regenerative medicine: current therapies and future directions. Proc Natl Acad Sci U S A 112:14452–14459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Martin CM, Ferdous A, Gallardo T, Humphries C, Sadek H, Caprioli A, Garcia JA, Szweda LI, Garry MG, Garry DJ (2008) Hypoxia-inducible factor-2alpha transactivates Abcg2 and promotes cytoprotection in cardiac side population cells. Circ Res 102:1075–1081

    Article  CAS  PubMed  Google Scholar 

  47. Masumoto H, Ikuno T, Takeda M, Fukushima H, Marui A, Katayama S, Shimizu T, Ikeda T, Okano T, Sakata R, Yamashita JK (2014) Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration. Sci Rep 4:6716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Matasic DS, Brenner C, London B (2018) Emerging potential benefits of modulating NAD(+) metabolism in cardiovascular disease. Am J Physiol Heart Circ Physiol 314:H839–H852

    Article  CAS  PubMed  Google Scholar 

  49. Mathiasen AB, Qayyum AA, Jorgensen E, Helqvist S, Fischer-Nielsen A, Kofoed KF, Haack-Sorensen M, Ekblond A, Kastrup J (2015) Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial). Eur Heart J 36:1744–1753

    Article  CAS  PubMed  Google Scholar 

  50. Mawad D, Figtree G, Gentile C (2017) Current technologies based on the knowledge of the stem cells microenvironments. Adv Exp Med Biol 1041:245–262

    Article  CAS  PubMed  Google Scholar 

  51. Menasche P, Hagege AA, Scorsin M, Pouzet B, Desnos M, Duboc D, Schwartz K, Vilquin JT, Marolleau JP (2001) Myoblast transplantation for heart failure. Lancet 357:279–280

    Article  CAS  PubMed  Google Scholar 

  52. Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, Vilquin JT, Marolleau JP, Seymour B, Larghero J, Lake S, Chatellier G, Solomon S, Desnos M, Hagege AA (2008) The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117:1189–1200

    Article  PubMed  Google Scholar 

  53. Menasche P, Vanneaux V, Hagege A, Bel A, Cholley B, Parouchev A, Cacciapuoti I, Al-Daccak R, Benhamouda N, Blons H, Agbulut O, Tosca L, Trouvin JH, Fabreguettes JR, Bellamy V, Charron D, Tartour E, Tachdjian G, Desnos M, Larghero J (2018) Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitors for Severe Ischemic Left Ventricular Dysfunction. J Am Coll Cardiol 71:429–438

    Article  PubMed  Google Scholar 

  54. Munzel T, Gori T, Keaney JF Jr, Maack C, Daiber A (2015) Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications. Eur Heart J 36:2555–2564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nobrega-Pereira S, Fernandez-Marcos PJ, Brioche T, Gomez-Cabrera MC, Salvador-Pascual A, Flores JM, Vina J, Serrano M (2016) G6PD protects from oxidative damage and improves healthspan in mice. Nat Commun 7:10894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    Article  CAS  PubMed  Google Scholar 

  57. Pastore A, Piemonte F (2013) Protein glutathionylation in cardiovascular diseases. Int J Mol Sci 14:20845–20876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Planavila A, Iglesias R, Giralt M, Villarroya F (2011) Sirt1 acts in association with PPARalpha to protect the heart from hypertrophy, metabolic dysregulation, and inflammation. Cardiovasc Res 90:276–284

    Article  CAS  PubMed  Google Scholar 

  59. Polonchuk L, Chabria M, Badi L, Hoflack JC, Figtree G, Davies MJ, Gentile C (2017) Cardiac spheroids as promising in vitro models to study the human heart microenvironment. Sci Rep 7:7005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Puente BN, Kimura W, Muralidhar SA, Moon J, Amatruda JF, Phelps KL, Grinsfelder D, Rothermel BA, Chen R, Garcia JA, Santos CX, Thet S, Mori E, Kinter MT, Rindler PM, Zacchigna S, Mukherjee S, Chen DJ, Mahmoud AI, Giacca M, Rabinovitch PS, Aroumougame A, Shah AM, Szweda LI, Sadek HA (2014) The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell 157:565–579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Qin F, Siwik DA, Pimentel DR, Morgan RJ, Biolo A, Tu VH, Kang YJ, Cohen RA, Colucci WS (2014) Cytosolic H2O2 mediates hypertrophy, apoptosis, and decreased SERCA activity in mice with chronic hemodynamic overload. Am J Physiol Heart Circ Physiol 306:H1453–H1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Redfield MM, Jacobsen SJ, Borlaug BA, Rodeheffer RJ, Kass DA (2005) Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation 112:2254–2262

    Article  PubMed  Google Scholar 

  63. Reinecke H, MacDonald GH, Hauschka SD, Murry CE (2000) Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. J Cell Biol 149:731–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sanada F, Kim J, Czarna A, Chan NY, Signore S, Ogorek B, Isobe K, Wybieralska E, Borghetti G, Pesapane A, Sorrentino A, Mangano E, Cappetta D, Mangiaracina C, Ricciardi M, Cimini M, Ifedigbo E, Perrella MA, Goichberg P, Choi AM, Kajstura J, Hosoda T, Rota M, Anversa P, Leri A (2014) c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy. Circ Res 114:41–55

    Article  CAS  PubMed  Google Scholar 

  65. Sattler S, Fairchild P, Watt FM, Rosenthal N, Harding SE (2017) The adaptive immune response to cardiac injury-the true roadblock to effective regenerative therapies? NPJ Regen Med 2:19

    Article  PubMed  PubMed Central  Google Scholar 

  66. Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, Wu TD, Guerquin-Kern JL, Lechene CP, Lee RT (2013) Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493:433–436

    Article  CAS  PubMed  Google Scholar 

  67. Stubbs SL, Crook JM, Morrison WA, Newcomb AE (2011) Toward clinical application of stem cells for cardiac regeneration. Heart Lung Circ 20:173–179

    Article  PubMed  Google Scholar 

  68. Tang YL, Zhu W, Cheng M, Chen L, Zhang J, Sun T, Kishore R, Phillips MI, Losordo DW, Qin G (2009) Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circ Res 104:1209–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. The Lancet E (2014) Expression of concern: the SCIPIO trial. Lancet 383:1279

    Article  Google Scholar 

  70. Tran C, Damaser MS (2015) Stem cells as drug delivery methods: application of stem cell secretome for regeneration. Adv Drug Deliv Rev 82–83:1–11

    Article  CAS  PubMed  Google Scholar 

  71. U.S. National Library of Medicine (2012) Compare the effects of single versus repeated intracoronary application of autologous bone marrow-derived mononuclear cells on mortality in patients with chronic post-infarction heart failure (REPEAT). Interventional (Clinical Trial)

    Google Scholar 

  72. U.S. National Library of Medicine (2018a) CardiAMP CMI randomized controlled pivotal trial in patients with chronic myocardial ischemia and refractory angina (CardiAMP CMI). Interventional 2018

    Google Scholar 

  73. U.S. National Library of Medicine (2018b) Combination of mesenchymal and C-kit+ cardiac stem cells as regenerative therapy for heart failure (CONCERT-HF). Interventional

    Google Scholar 

  74. U.S. National Library of Medicine (2018c) Efficacy and safety of allogeneic mesenchymal precursor cells (rexlemestrocel-L) for the treatment of heart failure. (DREAM HF-1). Interventional

    Google Scholar 

  75. U.S. National Library of Medicine (2018d) A study of VentriGel in post-MI patients

    Google Scholar 

  76. Valiente-Alandi I, Albo-Castellanos C, Herrero D, Arza E, Garcia-Gomez M, Segovia JC, Capecchi M, Bernad A (2015) Cardiac Bmi1(+) cells contribute to myocardial renewal in the murine adult heart. Stem Cell Res Ther 6:205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Vasan RS, Sullivan LM, D’Agostino RB, Roubenoff R, Harris T, Sawyer DB, Levy D, Wilson PW (2003) Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study. Ann Intern Med 139:642–648

    Article  CAS  PubMed  Google Scholar 

  78. Vicinanza C, Aquila I, Scalise M, Cristiano F, Marino F, Cianflone E, Mancuso T, Marotta P, Sacco W, Lewis FC, Couch L, Shone V, Gritti G, Torella A, Smith AJ, Terracciano CM, Britti D, Veltri P, Indolfi C, Nadal-Ginard B, Ellison-Hughes GM, Torella D (2017) Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification. Cell Death Differ 24:2101–2116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wang K, Ding R, Ha Y, Jia Y, Liao X, Wang S, Li R, Shen Z, Xiong H, Guo J, Jie W (2018a) Hypoxia-stressed cardiomyocytes promote early cardiac differentiation of cardiac stem cells through HIF-1alpha/Jagged1/Notch1 signaling. Acta Pharm Sin B 8:795–804

    Article  PubMed  PubMed Central  Google Scholar 

  80. Wang YL, Zhang G, Wang HJ, Tan YZ, Wang XY (2018b) Preinduction with bone morphogenetic protein-2 enhances cardiomyogenic differentiation of c-kit(+) mesenchymal stem cells and repair of infarcted myocardium. Int J Cardiol 265:173–180

    Article  PubMed  Google Scholar 

  81. Yamanaka S, Li J, Kania G, Elliott S, Wersto RP, Van Eyk J, Wobus AM, Boheler KR (2008) Pluripotency of embryonic stem cells. Cell Tissue Res 331:5–22

    Article  PubMed  Google Scholar 

  82. Yan B, Singla DK (2013) Transplanted induced pluripotent stem cells mitigate oxidative stress and improve cardiac function through the Akt cell survival pathway in diabetic cardiomyopathy. Mol Pharm 10:3425–3432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ye L, Chang YH, Xiong Q, Zhang P, Zhang L, Somasundaram P, Lepley M, Swingen C, Su L, Wendel JS, Guo J, Jang A, Rosenbush D, Greder L, Dutton JR, Zhang J, Kamp TJ, Kaufman DS, Ge Y, Zhang J (2014) Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell 15:750–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Yokota T, Wang Y (2016) p38 MAP kinases in the heart. Gene 575:369–376

    Article  CAS  PubMed  Google Scholar 

  85. Yoon HE, Kim EN, Kim MY, Lim JH, Jang IA, Ban TH, Shin SJ, Park CW, Chang YS, Choi BS (2016) Age-associated changes in the vascular renin-angiotensin system in mice. Oxid Med Cell Longev 2016:6731093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Kolling Institute, Royal North Shore Hospital, St Leonards, NSW, Australia

    Thomas Hansen, Gemma A. Figtree & Carmine Gentile

  2. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

    Thomas Hansen, Gemma A. Figtree & Carmine Gentile

  3. School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

    Soloman Saleh

Authors
  1. Thomas Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soloman Saleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gemma A. Figtree
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carmine Gentile
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gemma A. Figtree .

Editor information

Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Sciences, St Boniface Hospital, Albrechtsen Research Centre, Winnipeg, MB, Canada

    Naranjan S Dhalla

  3. Translational Health Science and Technology (THSTI), Department of Biotechnology, Faridabad, India

    Nirmal K Ganguly

  4. Translational Health Science and Technology (THSTI), Department of Biotechnology, Faridabad, India

    Madhu Dikshit

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hansen, T., Saleh, S., Figtree, G.A., Gentile, C. (2019). The Role of Redox Signalling in Cardiovascular Regeneration. In: Chakraborti, S., Dhalla, N., Ganguly, N., Dikshit, M. (eds) Oxidative Stress in Heart Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-13-8273-4_2

Download citation

Publish with us

Policies and ethics

Search

Navigation