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Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis

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An Erratum to this article was published on 29 May 2007

Abstract

Circulating levels of interleukin (IL)–6 and related cytokines are elevated in patients with congestive heart failure and after myocardial infarction. Serum IL-6 concentrations are related to decreasing functional status of these patients and provide important prognostic information.Moreover, in the failing human heart, multiple components of the IL-6- glycoprotein (gp)130 receptor system are impaired, implicating an important role of this system in cardiac pathophysiology.

Experimental studies have shown that the common receptor subunit of IL-6 cytokines is phosphorylated in response to pressure overload and myocardial infarction and that it subsequently activates at least three different downstream signaling pathways, the signal transducers and activators of transcription 1 and 3 (STAT1/3), the Src-homology tyrosine phosphatase 2 (SHP2)-Ras-ERK, and the PI3K-Akt system. Gp130 receptor mediated signaling promotes cardiomyocyte survival, induces hypertrophy, modulates cardiac extracellular matrix and cardiac function. In this regard, the gp130 receptor system and its main downstream mediator STAT3 play a key role in cardioprotection.

This review summarizes the current knowledge of IL-6 cytokines, gp130 receptor and STAT3 signaling in the heart exposed to physiological (aging, pregnancy) and pathophysiological stress (ischemia, pressure overload, inflammation and cardiotoxic agents) with a special focus on the potential role of individual IL-6 cytokines.

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References

  1. Ancey C, Corbi P, Froger J, Delwail A, Wijdenes J,Gascan H,Potreau D,Lecron JC (2002) Secretion of IL-6, IL-11 and LIF by human cardiomyocytes in primary culture. Cytokine 18:199–205

    PubMed  CAS  Google Scholar 

  2. Ancey C, Menet E, Corbi P, Fredj S, Garcia M, Rucker-Martin C, Bescond J, Morel F,Wijdenes J, Lecron JC, Potreau D (2003) Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation. Cardiovasc Res 59:78–85

    PubMed  CAS  Google Scholar 

  3. Antonicelli R, Olivieri F,Bonafe M,Cavallone L, Spazzafumo L,Marchegiani F, Cardelli M, Recanatini A, Testarmata P, Boemi M, Parati G, Franceschi C (2005) The interleukin-6–174 G→C promoter polymorphism is associated with a higher risk of death after an acute coronary syndrome in male elderly patients. Int J Cardiol 103:266–271

    PubMed  Google Scholar 

  4. Aoyama T, Takimoto Y, Pennica D, Inoue R, Shinoda E, Hattori R, Yui Y, Sasayama S (2000) Augmented expression of cardiotrophin-1 and its receptor component, gp130, in both left and right ventricles after myocardial infarction in the rat. J Mol Cell Cardiol 32:1821–1830

    PubMed  CAS  Google Scholar 

  5. Asai S, Saito Y, Kuwahara K, Mizuno Y, Yoshimura M, Higashikubo C, Tsuji T, Kishimoto I, Harada M, Hamanaka I, Takahashi N, Yasue H, Nakao K (2000) The heart is a source of circulating cardiotrophin- 1 in humans. Biochem Biophys Res Commun 279:320–323

    PubMed  CAS  Google Scholar 

  6. Aukrust P, Ueland T, Lien E, Bendtzen K, Muller F, Andreassen AK, Nordoy I, Aass H, Espevik T, Simonsen S, Froland SS, Gullestad L (1999) Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 83:376–382

    PubMed  CAS  Google Scholar 

  7. Bader A, Al-Dubai H,Weitzer G (2000) Leukemia inhibitory factor modulates cardiogenesis in embryoid bodies in opposite fashions. Circ Res 86:787–794

    PubMed  CAS  Google Scholar 

  8. Baines CP,Molkentin JD (2005) STRESS signaling pathways that modulate cardiac myocyte apoptosis. J Mol Cell Cardiol 38:47–62

    PubMed  CAS  Google Scholar 

  9. Bamber B, Reife RA, Haugen HS, Clegg CH (1998) Oncostatin M stimulates excessive extracellular matrix accumulation in a transgenic mouse model of connective tissue disease. J Mol Med 76:61–69

    PubMed  CAS  Google Scholar 

  10. Beckles DL,Mascareno E, Siddiqui MA (2006) Inhibition of Jak2 phosphorylation attenuates pressure overload cardiac hypertrophy. Vascul Pharmacol 45:350–357

    PubMed  CAS  Google Scholar 

  11. Benigni F, Sacco S, Pennica D, Ghezzi P (1996) Cardiotrophin-1 inhibits tumor necrosis factor production in the heart and serum of lipopolysaccharidetreated mice and in vitro in mouse blood cells. Am J Pathol 149:1847–1850

    PubMed  CAS  Google Scholar 

  12. Berry MF, Pirolli TJ, Jayasankar V, Morine KJ, Moise MA, Fisher O, Gardner TJ, Patterson PH, Woo YJ (2004) Targeted overexpression of leukemia inhibitory factor to preserve myocardium in a rat model of postinfarction heart failure. J Thorac Cardiovasc Surg 128:866–875

    PubMed  CAS  Google Scholar 

  13. Betz UA, Bloch W, van den Broek M, Yoshida K,Taga T,Kishimoto T,Addicks K,Rajewsky K,Muller W (1998) Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic,immunological,hepatic, and pulmonary defects. J Exp Med 188:1955–1965

    PubMed  CAS  Google Scholar 

  14. Bhat GJ, Abraham ST, Baker KM (1996) Angiotensin II interferes with interleukin 6-induced Stat3 signaling by a pathway involving mitogen-activated protein kinase kinase 1. J Biol Chem 271:22447–22452

    PubMed  CAS  Google Scholar 

  15. Birks EJ, Latif N, Owen V, Bowles C, Felkin LE,Mullen AJ, Khaghani A, Barton PJ,Polak JM,Pepper JR,Banner NR, Yacoub MH (2001) Quantitative myocardial cytokine expression and activation of the apoptotic pathway in patients who require left ventricular assist devices. Circulation 104:I233–240

    PubMed  CAS  Google Scholar 

  16. Booz GW, Day JN, Baker KM (2002) Interplay between the cardiac renin angiotensin system and JAK-STAT signaling: role in cardiac hypertrophy, ischemia/reperfusion dysfunction, and heart failure. J Mol Cell Cardiol 34:1443–1453

    PubMed  CAS  Google Scholar 

  17. Bossowska A, Kiersnowska-Rogowska B, Bossowski A, Galar B, Sowinski P (2003) Cytokines in patients with ischaemic heart disease or myocardial infarction. Kardiol Pol 59:105–114

    PubMed  Google Scholar 

  18. Brar BK, Stephanou A, Liao Z, O’Leary RM, Pennica D, Yellon DM, Latchman DS (2001) Cardiotrophin-1 can protect cardiac myocytes from injury when added both prior to simulated ischaemia and at reoxygenation. Cardiovasc Res 51:265–274

    PubMed  CAS  Google Scholar 

  19. Brar BK, Stephanou A, Pennica D, Latchman DS (2001) CT-1 mediated cardioprotection against ischaemic reoxygenation injury is mediated by PI3 kinase, Akt and MEK1/2 pathways. Cytokine 16:93–96

    PubMed  CAS  Google Scholar 

  20. Briest W, Rassler B, Deten A, Leicht M, Morwinski R, Neichel D, Wallukat G, Ziegelhoffer T, Zimmer HG (2003) Norepinephrine- induced interleukin-6 increase in rat hearts: differential signal transduction in myocytes and nonmyocytes. Pflugers Arch 446:437–446

    PubMed  CAS  Google Scholar 

  21. Buzas K,Megyeri K,Hogye M, Csanady M, Bogats G,Mandi Y (2004) Comparative study of the roles of cytokines and apoptosis in dilated and hypertrophic cardiomyopathies. Eur Cytokine Netw 15:53–59

    PubMed  CAS  Google Scholar 

  22. Chen X, Vinkemeier U, Zhao Y, Jeruzalmi D, Darnell JE, Jr., Kuriyan J (1998) Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell 93:827–839

    PubMed  CAS  Google Scholar 

  23. Chin BS, Blann AD, Gibbs CR, Chung NA, Conway DG, Lip GY (2003) Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand factor, tissue factor and vascular endothelial growth factor levels in congestive heart failure. Eur J Clin Invest 33:941–948

    PubMed  CAS  Google Scholar 

  24. Craig R,Wagner M, McCardle T, Craig AG, Glembotski CC (2001) The cytoprotective effects of the glycoprotein 130 receptor-coupled cytokine, cardiotrophin- 1, require activation of NFkappa B. J Biol Chem 276:37621–37629

    PubMed  CAS  Google Scholar 

  25. David M, Chen HE, Goelz S, Larner AC, Neel BG (1995) Differential regulation of the alpha/beta interferon-stimulated Jak/Stat pathway by the SH2 domaincontaining tyrosine phosphatase SHPTP1.Mol Cell Biol 15:7050–7058

    PubMed  CAS  Google Scholar 

  26. Dawn B, Xuan YT, Guo Y, Rezazadeh A, Stein AB,Hunt G,Wu WJ,Tan W, Bolli R (2004) IL-6 plays an obligatory role in late preconditioning via JAK-STAT signaling and upregulation of iNOS and COX-2. Cardiovasc Res 64:61–71

    PubMed  CAS  Google Scholar 

  27. Ebelt H, Jungblut M, Zhang Y, Kubin T, Kostin S, Technau A, Oustanina S, Niebrugge S, Lehmann J, Werdan K, Braun T (2007) Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive cytokines. Stem Cells 25:236–244

    PubMed  CAS  Google Scholar 

  28. Eiken HG,Oie E,Damas JK,Yndestad A, Bjerkeli V, Aass H, Simonsen S, Geiran OR, Tonnessen T, Christensen G, Froland SS, Gullestad L, Attramadal H, Aukrust P (2001) Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure. Eur J Clin Invest 31:389–397

    PubMed  CAS  Google Scholar 

  29. El-Adawi H, Deng L, Tramontano A, Smith S, Mascareno E, Ganguly K, Castillo R, El-Sherif N (2003) The functional role of the JAK-STAT pathway in post-infarction remodeling.Cardiovasc Res 57:129–138

    PubMed  CAS  Google Scholar 

  30. Fearon U, Mullan R, Markham T, Connolly M, Sullivan S, Poole AR, FitzGerald O, Bresnihan B,Veale DJ (2006) Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures. Arthritis Rheum 54:3152–3162

    PubMed  CAS  Google Scholar 

  31. Fischer P, Lehmann U, Sobota RM, Schmitz J, Niemand C, Linnemann S, Haan S, Behrmann I, Yoshimura A, Johnston JA,Muller-Newen G,Heinrich PC, Schaper F (2004) The role of the inhibitors of interleukin-6 signal transduction SHP2 and SOCS3 for desensitization of interleukin-6 signalling. Biochem J 378:449–460

    PubMed  CAS  Google Scholar 

  32. Florholmen G,Aas V, Rustan AC, Lunde PK, Straumann N, Eid H, Odegaard A, Dishington H, Andersson KB, Christensen G (2004) Leukemia inhibitory factor reduces contractile function and induces alterations in energy metabolism in isolated cardiomyocytes. J Mol Cell Cardiol 37:1183–1193

    PubMed  CAS  Google Scholar 

  33. Foshay K,Rodriguez G,Hoel B,Narayan J, Gallicano GI (2005) JAK2/STAT3 directs cardiomyogenesis within murine embryonic stem cells in vitro. Stem Cells 23:530–543

    PubMed  CAS  Google Scholar 

  34. Freed DH, Borowiec AM,Angelovska T, Dixon IM (2003) Induction of protein synthesis in cardiac fibroblasts by cardiotrophin- 1: integration of multiple signaling pathways. Cardiovasc Res 60:365–375

    PubMed  CAS  Google Scholar 

  35. Freed DH,Cunnington RH,Dangerfield AL, Sutton JS, Dixon IM (2005) Emerging evidence for the role of cardiotrophin- 1 in cardiac repair in the infarcted heart. Cardiovasc Res 65:782–792

    PubMed  CAS  Google Scholar 

  36. Freed DH, Moon MC, Borowiec AM, Jones SC, Zahradka P, Dixon IM (2003) Cardiotrophin-1: expression in experimental myocardial infarction and potential role in post-MI wound healing. Mol Cell Biochem 254:247–256

    PubMed  CAS  Google Scholar 

  37. Fuchs M, Hilfiker A, Kaminski K, Hilfiker- Kleiner D, Guener Z, Klein G, Podewski E, Schieffer B, Rose-John S, Drexler H (2003) Role of interleukin-6 for LV remodeling and survival after experimental myocardial infarction. Faseb J 17:2118–2120

    PubMed  CAS  Google Scholar 

  38. Funamoto M, Fujio Y, Kunisada K, Negoro S, Tone E, Osugi T, Hirota H, Izumi M, Yoshizaki K, Walsh K, Kishimoto T, Yamauchi-Takihara K (2000) Signal transducer and activator of transcription 3 is required for glycoprotein 130-mediated induction of vascular endothelial growth factor in cardiac myocytes. J Biol Chem 275:10561–10566

    PubMed  CAS  Google Scholar 

  39. Gaussin V, Van de Putte T, Mishina Y, Hanks MC, Zwijsen A, Huylebroeck D, Behringer RR, Schneider MD (2002) Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3.Proc Natl Acad Sci U S A 99:2878–2883

    PubMed  CAS  Google Scholar 

  40. Gonzalez A, Lopez B, Martin-Raymondi D, Lozano E, Varo N, Barba J, Serrano M, Diez J (2005) Usefulness of plasma cardiotrophin- 1 in assessment of left ventricular hypertrophy regression in hypertensive patients. J Hypertens 23:2297–2304

    PubMed  CAS  Google Scholar 

  41. Grenier A, Combaux D, Chastre J, Gougerot-Pocidalo MA, Gibert C, Dehoux M, Chollet-Martin S (2001) Oncostatin M production by blood and alveolar neutrophils during acute lung injury. Lab Invest 81:133–141

    PubMed  CAS  Google Scholar 

  42. Gritman K, Van Winkle DM, Lorentz CU,Pennica D,Habecker BA (2006) The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response. Cytokine 36:9–16

    PubMed  CAS  Google Scholar 

  43. Gwechenberger M,Moertl D, Pacher R, Huelsmann M (2004) Oncostatin-M in myocardial ischemia/reperfusion injury may regulate tissue repair. Croat Med J 45:149–157

    PubMed  Google Scholar 

  44. Gwechenberger M, Pacher R, Berger R, Zorn G, Moser P, Stanek B, Huelsmann M (2005) Comparison of soluble glycoprotein 130 and cardiac natriuretic peptides as long-term predictors of heart failure progression. J Heart Lung Transplant 24:2190–2195

    PubMed  Google Scholar 

  45. Haspel RL, Darnell JE, Jr. (1999) A nuclear protein tyrosine phosphatase is required for the inactivation of STAT1. Proc Natl Acad Sci USA 96:10188–10193

    PubMed  CAS  Google Scholar 

  46. Hattori R, Maulik N, Otani H, Zhu L, Cordis G, Engelman RM, Siddiqui MA, Das DK (2001) Role of STAT3 in ischemic preconditioning. J Mol Cell Cardiol 33:1929–1936

    PubMed  CAS  Google Scholar 

  47. Heinrich PC, Behrmann I,Haan S,Hermanns HM,Muller-Newen G, Schaper F (2003) Principles of interleukin (IL)–6- type cytokine signalling and its regulation. Biochem J 374:1–20

    PubMed  CAS  Google Scholar 

  48. Heinrich PC, Behrmann I, Muller- Newen G,Schaper F,Graeve L (1998) Interleukin- 6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J 334 (Pt 2):297–314

    PubMed  CAS  Google Scholar 

  49. Heinrich PC, Bode J, Decker M, Graeve L,Martens A,Muller-Newen G, Pflanz S, Schaper F, Schmitz J (2001) Termination and modulation of IL-6-type cytokine signaling. Adv Exp Med Biol 495:153–160

    PubMed  CAS  Google Scholar 

  50. Hilfiker-Kleiner D,Hilfiker A,Drexler H (2005) Many good reasons to have STAT3 in the heart. Pharmacol Ther 107:131–137

    PubMed  CAS  Google Scholar 

  51. Hilfiker-Kleiner D,Hilfiker A, Fuchs M, Kaminski K, Schaefer A, Schieffer B, Hillmer A, Schmiedl A, Ding Z, Podewski E, Poli V, Schneider MD, Schulz R,Park JK,Wollert KC,Drexler H (2004) Signal transducer and activator of transcription 3 is required for myocardial capillary growth, control of interstitial matrix deposition,and heart protection from ischemic injury. Circ Res 95:187–195

    PubMed  CAS  Google Scholar 

  52. Hilfiker-Kleiner D, Kaminski K, Podewski E, Bonda T, Schaefer A, Sliwa K, Forster O, Quint A, Landmesser U, Doerries C, Luchtefeld M, Poli V, Schneider MD, Balligand JL, Desjardins F, Ansari A, Struman I, Nguyen NQ, Zschemisch NH, Klein G, Heusch G, Schulz R,Hilfiker A, Drexler H (2007) A Cathepsin D-Cleaved 16 kDa Form of Prolactin Mediates Postpartum Cardiomyopathy. Cell 128:589–600

    PubMed  CAS  Google Scholar 

  53. Hilfiker-Kleiner D,Limbourg A,Drexler H (2005) STAT3-mediated activation of myocardial capillary growth. Trends Cardiovasc Med 15:152–157

    PubMed  CAS  Google Scholar 

  54. Hirano T, Nakajima K, Hibi M (1997) Signaling mechanisms through gp130: a model of the cytokine system. Cytokine Growth Factor Rev 8:241–252

    PubMed  CAS  Google Scholar 

  55. Hiraoka E, Kawashima S, Takahashi T, Rikitake Y, Hirase T, Yokoyama M (2003) PI 3-kinase-Akt-p70 S6 kinase in hypertrophic responses to leukemia inhibitory factor in cardiac myocytes. Kobe J Med Sci 49:25–37

    PubMed  CAS  Google Scholar 

  56. Hirota H, Chen J, Betz UA, Rajewsky K, Gu Y, Ross J, Jr., Muller W, Chien KR (1999) Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 97:189–198

    PubMed  CAS  Google Scholar 

  57. Hirota H, Izumi M, Hamaguchi T, Sugiyama S, Murakami E, Kunisada K, Fujio Y, Oshima Y, Nakaoka Y, Yamauchi- Takihara K (2004) Circulating interleukin-6 family cytokines and their receptors in patients with congestive heart failure. Heart Vessels 19:237–241

    PubMed  Google Scholar 

  58. Hirota H,Yoshida K, Kishimoto T, Taga T (1995) Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci USA 92:4862–4866

    PubMed  CAS  Google Scholar 

  59. Hishinuma S, Funamoto M, Fujio Y,Kunisada K, Yamauchi-Takihara K (1999) Hypoxic stress induces cardiotrophin-1 expression in cardiac myocytes. Biochem Biophys Res Commun 264:436–440

    PubMed  CAS  Google Scholar 

  60. Humphries SE, Luong LA, Ogg MS, Hawe E, Miller GJ (2001) The interleukin- 6–174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 22:2243–2252

    PubMed  CAS  Google Scholar 

  61. Iemitsu M, Maeda S, Miyauchi T, Matsuda M, Tanaka H (2005) Gene expression profiling of exercise-induced cardiac hypertrophy in rats. Acta Physiol Scand 185:259–270

    PubMed  CAS  Google Scholar 

  62. Ihn H, Tamaki K (2000) Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated protein kinase-dependent pathway. J Immunol 165:2149–2155

    PubMed  CAS  Google Scholar 

  63. Ishikawa M, Saito Y, Miyamoto Y, Harada M, Kuwahara K, Ogawa E, Nakagawa O,Hamanaka I, Kajiyama N, Takahashi N, Masuda I, Hashimoto T, Sakai O, Hosoya T, Nakao K (1999) A heart-specific increase in cardiotrophin- 1 gene expression precedes the establishment of ventricular hypertrophy in genetically hypertensive rats. J Hypertens 17:807–816

    PubMed  CAS  Google Scholar 

  64. Jacoby JJ, Kalinowski A, Liu MG, Zhang SS, Gao Q, Chai GX, Ji L, Iwamoto Y,Li E, Schneider M, Russell KS, Fu XY (2003) Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age. Proc Natl Acad Sci U S A 100:12929–12934

    PubMed  CAS  Google Scholar 

  65. Jamshidi Y,Zourlidou A,Carroll CJ,Sinclair J, Latchman DS (2004) Signaltransduction pathways involved in the hypertrophic effect of hsp56 in neonatal cardiomyocytes. J Mol Cell Cardiol 36:381–392

    PubMed  CAS  Google Scholar 

  66. Jin H,Yang R, Keller GA, Ryan A, Ko A, Finkle D, Swanson TA, Li W, Pennica D, Wood WI, Paoni NF (1996) In vivo effects of cardiotrophin-1. Cytokine 8:920–926

    PubMed  CAS  Google Scholar 

  67. Jougasaki M, Leskinen H, Larsen AM, Cataliotti A, Chen HH, Burnett JC, Jr. (2003) Leukemia inhibitory factor is augmented in the heart in experimental heart failure. Eur J Heart Fail 5:137–145

    PubMed  CAS  Google Scholar 

  68. Jougasaki M, Tachibana I, Luchner A, Leskinen H, Redfield MM, Burnett JC, Jr. (2000) Augmented cardiac cardiotrophin- 1 in experimental congestive heart failure. Circulation 101:14–17

    PubMed  CAS  Google Scholar 

  69. Kanda T, Takahashi T (2004) Interleukin- 6 and cardiovascular diseases. Jpn Heart J 45:183–193

    PubMed  CAS  Google Scholar 

  70. Kaneko K, Kanda T, Yokoyama T, Nakazato Y, Iwasaki T, Kobayashi I, Nagai R (1997) Expression of interleukin- 6 in the ventricles and coronary arteries of patients with myocardial infarction. Res Commun Mol Pathol Pharmacol 97:3–12

    PubMed  CAS  Google Scholar 

  71. Kato T, Sano M, Miyoshi S, Sato T, Hakuno D, Ishida H, Kinoshita- Nakazawa H, Fukuda K,Ogawa S (2000) Calmodulin kinases II and IV and calcineurin are involved in leukemia inhibitory factor-induced cardiac hypertrophy in rats. Circ Res 87:937–945

    PubMed  CAS  Google Scholar 

  72. Keller ET,Wanagat J, Ershler WB (1996) Molecular and cellular biology of interleukin- 6 and its receptor. Front Biosci 1:d340–357

    PubMed  CAS  Google Scholar 

  73. Khan SQ, Kelly D, Quinn P, Davies JE, Ng LL (2006) Cardiotrophin-1 predicts death or heart failure following acute myocardial infarction. J Card Fail 12:635–640

    PubMed  CAS  Google Scholar 

  74. Kishimoto T (1994) Signal transduction through homo- or heterodimers of gp130. Stem Cells 12(Suppl 1):37–44; discussion 44–35

    PubMed  Google Scholar 

  75. Kodama H, Fukuda K, Pan J,Makino S, Baba A, Hori S, Ogawa S (1997) Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, activates the JAK/STAT pathway in rat cardiomyocytes. Circ Res 81:656–663

    PubMed  CAS  Google Scholar 

  76. Kodama H, Fukuda K, Pan J, Sano M, Takahashi T, Kato T,Makino S,Manabe T, Murata M, Ogawa S (2000) Significance of ERK cascade compared with JAK/STAT and PI3-K pathway in gp130- mediated cardiac hypertrophy. Am J Physiol Heart Circ Physiol 279: H1635–1644

    PubMed  CAS  Google Scholar 

  77. Kunisada K,Hirota H,Fujio Y,Matsui H, Tani Y, Yamauchi-Takihara K, Kishimoto T (1996) Activation of JAK-STAT and MAP kinases by leukemia inhibitory factor through gp130 in cardiac myocytes. Circulation 94:2626–2632

    PubMed  CAS  Google Scholar 

  78. Kunisada K, Negoro S, Tone E, Funamoto M,Osugi T,Yamada S,Okabe M, Kishimoto T, Yamauchi-Takihara K (2000) Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin- induced cardiomyopathy. Proc Natl Acad Sci USA 97:315–319

    PubMed  CAS  Google Scholar 

  79. Kunisada K, Tone E, Fujio Y, Matsui H, Yamauchi-Takihara K, Kishimoto T (1998) Activation of gp130 transduces hypertrophic signals via STAT3 in cardiac myocytes. Circulation 98:346–352

    PubMed  CAS  Google Scholar 

  80. Kurdi M, Randon J, Cerutti C, Bricca G (2005) Increased expression of IL-6 and LIF in the hypertrophied left ventricle of TGR(mRen2)27 and SHR rats. Mol Cell Biochem 269:95–101

    PubMed  CAS  Google Scholar 

  81. Kuwahara K, Saito Y, Kishimoto I, Miyamoto Y, Harada M, Ogawa E, Hamanaka I, Kajiyama N, Takahashi N, Izumi T, Kawakami R, Nakao K (2000) Cardiotrophin-1 phosphorylates akt and BAD, and prolongs cell survival via a PI3K-dependent pathway in cardiac myocytes. J Mol Cardiol 32:1385–1394

    CAS  Google Scholar 

  82. Lafontant PJ, Burns AR, Donnachie E, Haudek SB, Smith CW, Entman ML (2006) Oncostatin M differentially regulates CXC chemokines in mouse cardiac fibroblasts. Am J Physiol Cell Physiol 291:C18–26

    PubMed  CAS  Google Scholar 

  83. Latchman DS (2000) Cardiotrophin-1: a novel cytokine and its effects in the heart and other tissues. Pharmacol Ther 85:29–37

    PubMed  CAS  Google Scholar 

  84. Lehmann U, Schmitz J,Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG,Heinrich PC, Schaper F (2003) SHP2 and SOCS3 contribute to Tyr-759- dependent attenuation of interleukin-6 signaling through gp130. J Biol Chem 278:661–671

    PubMed  CAS  Google Scholar 

  85. Li YJ, Cui W, Tian ZJ,Hao YM, Du J, Liu F, Zhang H, Zu XG, Liu SY, Xie RQ,Yang XH, Wu YZ, Chen L, An W (2004) Crosstalk between ERK1/2 and STAT3 in the modulation of cardiomyocyte hypertrophy induced by cardiotrophin- 1. Chin Med J (Engl) 117:1135–1142

    PubMed  CAS  Google Scholar 

  86. Lopez B, Gonzalez A, Lasarte JJ, Sarobe P, Borras F, Diaz A, Barba J, Tomas L, Lozano E,Serrano M,Varo N,Beloqui O, Fortuno MA, Diez J (2005) Is plasma cardiotrophin-1 a marker of hypertensive heart disease? J Hypertens 23:625–632

    Article  PubMed  CAS  Google Scholar 

  87. Lopez N, Diez J, Fortuno MA (2005) Characterization of the protective effects of cardiotrophin-1 against non-ischemic death stimuli in adult cardiomyocytes. Cytokine 30:282–292

    PubMed  CAS  Google Scholar 

  88. Lopez N,Diez J,Fortuno MA (2006) Differential hypertrophic effects of cardiotrophin- 1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats. J Mol Cell Cardiol 41:902–913

    PubMed  CAS  Google Scholar 

  89. Maeda K, Tsutamoto T, Wada A, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T,Kinoshita M (2000) High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure. J Am Coll Cardiol 36:1587–1593

    PubMed  CAS  Google Scholar 

  90. Mascareno E, Beckles DL, Siddiqui MA (2005) Janus kinase-2 signaling mediates apoptosis in rat cardiomyocytes. Vascul Pharmacol 43:327–335

    PubMed  CAS  Google Scholar 

  91. Masson S, Latini R, Bevilacqua M,Vago T, Sessa F, Torri M, Anesini A, Salio M, Pasotti E,Agnello D, Santoro L, Catania A, Ghezzi P, Moccetti T, Maggioni AP (1998) Within-patient variability of hormone and cytokine concentrations in heart failure. Pharmacol Res 37:213–217

    PubMed  CAS  Google Scholar 

  92. Matsui H,Fujio Y,Kunisada K,Hirota H, Yamauchi-Takihara K (1996) Leukemia inhibitory factor induces a hypertrophic response mediated by gp130 in murine cardiac myocytes. Res Commun Mol Pathol Pharmacol 93:149–162

    PubMed  CAS  Google Scholar 

  93. Matsushita K, Iwanaga S,Oda T,Kimura K, Shimada M, Sano M, Umezawa A, Hata J, Ogawa S (2005) Interleukin- 6/soluble interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis. Lab Invest 85:1210–1223

    PubMed  CAS  Google Scholar 

  94. Meldrum DR, Meng X, Sheridan BC, McIntyre RC, Jr., Harken AH, Banerjee A (1998) Tissue-specific protein kinase C isoforms differentially mediate macrophage TNFalpha and IL-1beta production. Shock 9:256–260

    PubMed  CAS  Google Scholar 

  95. Miyata S, Takemura G, Kawase Y, Li Y, Okada H, Maruyama R, Ushikoshi H, Esaki M, Kanamori H, Li L, Misao Y, Tezuka A, Toya-Oka T, Minatoguchi S, Fujiwara T, Fujiwara H (2006) Autophagic cardiomyocyte death in cardiomyopathic hamsters and its prevention by granulocyte colony-stimulating factor.Am J Pathol 168:386–397

    PubMed  CAS  Google Scholar 

  96. Murakami M, Hibi M, Nakagawa N, Nakagawa T,Yasukawa K,Yamanishi K, Taga T, Kishimoto T (1993) IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science 260:1808–1810

    PubMed  CAS  Google Scholar 

  97. Murata M, Fukuda K, Ishida H, Miyoshi S, Koura T, Kodama H, Nakazawa HK, Ogawa S (1999) Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, enhances L-type Ca2+ current and (Ca2+)i transient in cardiomyocytes. J Mol Cell Cardiol 31:237–245

    PubMed  CAS  Google Scholar 

  98. Nakaoka Y, Nishida K, Fujio Y, Izumi M,Terai K,Oshima Y,Sugiyama S,Matsuda S, Koyasu S, Yamauchi-Takihara K,Hirano T,Kawase I,Hirota H (2003) Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes. Circ Res 93:221–229

    PubMed  CAS  Google Scholar 

  99. Negoro S, Kunisada K, Fujio Y, Funamoto M, Darville MI, Eizirik DL, Osugi T, Izumi M, Oshima Y, Nakaoka Y, Hirota H, Kishimoto T, Yamauchi- Takihara K (2001) Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hypoxia/reoxygenation-induced oxidative stress through the upregulation of manganese superoxide dismutase. Circulation 104:979–981

    PubMed  CAS  Google Scholar 

  100. Nemoto S, Sheng Z, Lin A (1998) Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on cardiomyocyte hypertrophy. Mol Cell Biol 18:3518–3526

    PubMed  CAS  Google Scholar 

  101. Nian M, Lee P, Khaper N, Liu P (2004) Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res 94:1543–1553

    PubMed  CAS  Google Scholar 

  102. Oh H, Fujio Y,Kunisada K, et al. (1998) Activation of phosphatidylinositol 3- kinase through glycoprotein 130 induces protein kinase B and p70, S6 kinase phosphorylation in cardiac myocytes. J Biol Chem 273:9703–9710

    PubMed  CAS  Google Scholar 

  103. Olivier C, Auguste P, Chabbert M, Lelievre E, Chevalier S, Gascan H (2000) Identification of a gp130 cytokine receptor critical site involved in oncostatin M response. J Biol Chem 275:5648–5656

    PubMed  CAS  Google Scholar 

  104. Omura T, Yoshiyama M, Ishikura F, Kobayashi H, Takeuchi K, Beppu S, Yoshikawa J (2001) Myocardial ischemia activates the JAK-STAT pathway through angiotensin II signaling in in vivo myocardium of rats. J Mol Cell Cardiol 33:307–316

    PubMed  CAS  Google Scholar 

  105. Orus J, Roig E, Perez-Villa F, Pare C, Azqueta M, Filella X, Heras M, Sanz G (2000) Prognostic value of serum cytokines in patients with congestive heart failure. J Heart Lung Transplant 19:419–425

    PubMed  CAS  Google Scholar 

  106. Oshima Y, Fujio Y,Nakanishi T, Itoh N, Yamamoto Y, Negoro S, Tanaka K, Kishimoto T,Kawase I,Azuma J (2005) STAT3 mediates cardioprotection against ischemia/reperfusion injury through metallothionein induction in the heart. Cardiovasc Res 65:428–435

    PubMed  CAS  Google Scholar 

  107. Osugi T, Oshima Y, Fujio Y, Funamoto M,Yamashita A,Negoro S,Kunisada K, Izumi M, Nakaoka Y, Hirota H, Okabe M, Yamauchi-Takihara K, Kawase I, Kishimoto T (2002) Cardiac-specific activation of signal transducer and activator of transcription 3 promotes vascular formation in the heart. J Biol Chem 277:6676–6681

    PubMed  CAS  Google Scholar 

  108. Pan J, Fukuda K, Kodama H, Sano M, Takahashi T,Makino S,Kato T,Manabe T,Hori S, Ogawa S (1998) Involvement of gp130-mediated signaling in pressure overload-induced activation of the JAK/STAT pathway in rodent heart. Heart Vessels 13:199–208

    PubMed  CAS  Google Scholar 

  109. Pemberton CJ, Raudsepp SD, Yandle TG, Cameron VA, Richards AM (2005) Plasma cardiotrophin-1 is elevated in human hypertension and stimulated by ventricular stretch. Cardiovasc Res 68:109–117

    PubMed  CAS  Google Scholar 

  110. Pennica D,Wood WI, Chien KR (1996) Cardiotrophin-1: a multifunctional cytokine that signals via LIF receptorgp 130 dependent pathways. Cytokine Growth Factor Rev 7:81–91

    PubMed  CAS  Google Scholar 

  111. Petersen AM, Pedersen BK (2006) The role of IL-6 in mediating the anti-inflammatory effects of exercise. J Physiol Pharmacol 57 (Suppl 10):43–51

    PubMed  Google Scholar 

  112. Plun-Favreau H, Perret D, Diveu C, Froger J, Chevalier S, Lelievre E, Gascan H, Chabbert M (2003) Leukemia inhibitory factor (LIF), cardiotrophin- 1, and oncostatin M share structural binding determinants in the immunoglobulin- like domain of LIF receptor. J Biol Chem 278:27169–27179

    PubMed  CAS  Google Scholar 

  113. Podewski EK, Hilfiker-Kleiner D, Hilfiker A, Morawietz H, Lichtenberg A, Wollert KC, Drexler H (2003) Alterations in Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling in patients with end-stage dilated cardiomyopathy. Circulation 107:798–802

    PubMed  CAS  Google Scholar 

  114. Pourtau J,Mirshahi F,Li H,Muraine M, Vincent L, Tedgui A,Vannier JP, Soria J,Vasse M, Soria C (1999) Cyclooxygenase- 2 activity is necessary for the angiogenic properties of oncostatin M FEBS Lett 459:453–457

  115. Railson J, Lawrence K, Stephanou A, Brar B, Pennica D, Latchman D (2000) Cardiotrophin-1 reduces stress-induced heat shock protein production in cardiac myocytes. Cytokine 12:1741–1744

    PubMed  CAS  Google Scholar 

  116. Railson JE, Liao Z, Brar BK, Buddle JC, Pennica D, Stephanou A,Latchman DS (2002) Cardiotrophin-1 and urocortin cause protection by the same pathway and hypertrophy via distinct pathways in cardiac myocytes. Cytokine 17:243–253

    PubMed  CAS  Google Scholar 

  117. Raju SV, Zheng M, Schuleri KH, Phan AC, Bedja D, Saraiva RM, Yiginer O, Vandegaer K, Gabrielson KL, O’Donnell C P, Berkowitz DE, Barouch LA, Hare JM (2006) Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptinresistant obesity. Proc Natl Acad Sci USA 103:4222–4227

    PubMed  CAS  Google Scholar 

  118. Rattazzi M, Puato M, Faggin E, Bertipaglia B, Zambon A, Pauletto P (2003) C-reactive protein and interleukin-6 in vascular disease: culprits or passive bystanders? J Hypertens 21:1787–1803

    PubMed  CAS  Google Scholar 

  119. Roig E, Orus J, Pare C, Azqueta M, Filella X, Perez-Villa F, Heras M, Sanz G (1998) Serum interleukin-6 in congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 82:688–690, A688

    PubMed  CAS  Google Scholar 

  120. Roy S, Khanna S, Kuhn DE, Rink C, Williams WT, Zweier JL, Sen CK (2006) Transcriptome analysis of the ischemia-reperfused remodeling myocardium: temporal changes in inflammation and extracellular matrix. Physiol Genomics 25:364–374

    PubMed  CAS  Google Scholar 

  121. Saito M, Yoshida K, Hibi M, Taga T, Kishimoto T (1992) Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo. J Immunol 148:4066–4071

    PubMed  CAS  Google Scholar 

  122. Sano M, Fukuda K, Kodama H, Pan J, Saito M, Matsuzaki J, Takahashi T, Makino S, Kato T, Ogawa S (2000) Interleukin- 6 family of cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes. J Biol Chem 275:29717–29723

    PubMed  CAS  Google Scholar 

  123. Sano M, Fukuda K, Sato T, Kawaguchi H, Suematsu M, Matsuda S, Koyasu S, Matsui H, Yamauchi-Takihara K, Harada M, Saito Y, Ogawa S (2001) ERK and p38 MAPK, but not NF-kappaB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin II in cardiac fibroblasts. Circ Res 89:661–669

    PubMed  CAS  Google Scholar 

  124. Sarkar S,Vellaichamy E, Young D, Sen S (2004) Influence of cytokines and growth factors in ANG II-mediated collagen upregulation by fibroblasts in rats: role of myocytes. Am J Physiol Heart Circ Physiol 287:H107–117

    PubMed  CAS  Google Scholar 

  125. Scaffidi AK,Mutsaers SE,Moodley YP, McAnulty RJ, Laurent GJ, Thompson PJ, Knight DA (2002) Oncostatin M stimulates proliferation,induces collagen production and inhibits apoptosis of human lung fibroblasts. Br J Pharmacol 136:793–801

    PubMed  CAS  Google Scholar 

  126. Schmidt BM, Schmieder RE (2005) Cardiotrophin: its importance as a pathogenetic factor and as a measure of left ventricular hypertrophy. J Hypertens 23:2151–2153

    PubMed  CAS  Google Scholar 

  127. Sheng Z, Knowlton K, Chen J, Hoshijima M, Brown JH, Chien KR (1997) Cardiotrophin 1 (CT-1) inhibition of cardiac myocyte apoptosis via a mitogen- activated protein kinase-dependent pathway.Divergence from downstream CT-1 signals for myocardial cell hypertrophy. J Biol Chem 272:5783–5791

    PubMed  CAS  Google Scholar 

  128. Sheng Z, Pennica D,Wood WI, Chien KR (1996) Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival. Development 122:419–428

    PubMed  CAS  Google Scholar 

  129. Smith RM,Suleman N,Lacerda L,Opie LH, Akira S, Chien KR, Sack MN (2004) Genetic depletion of cardiac myocyte STAT-3 abolishes classical preconditioning. Cardiovasc Res 63:611–616

    PubMed  CAS  Google Scholar 

  130. Somasundaram R, Ruehl M, Schaefer B, Schmid M, Ackermann R, Riecken EO, Zeitz M, Schuppan D (2002) Interstitial collagens I, III, and VI sequester and modulate the multifunctional cytokine oncostatin MJ Biol Chem 277: 3242–3246

    Google Scholar 

  131. Starr R,Hilton DJ (1999) Negative regulation of the JAK/STAT pathway. BioEssays 21:47–52

    PubMed  CAS  Google Scholar 

  132. Stephanou A, Brar B, Heads R, Knight RD,Marber MS, Pennica D, Latchman DS (1998) Cardiotrophin-1 induces heat shock protein accumulation in cultured cardiac cells and protects them from stressful stimuli. J Mol Cell Cardiol 30:849–855

    PubMed  CAS  Google Scholar 

  133. Strand K, Murray J, Aziz S, Ishida A, Rahman S, Patel Y, Cardona C, Hammond WP, Savidge G, Wijelath ES (2000) Induction of the urokinase plasminogen activator system by oncostatin M promotes endothelial migration. J Cell Biochem 79:239–248

    PubMed  CAS  Google Scholar 

  134. Takahashi N, Saito Y, Kuwahara K, Harada M, Tanimoto K, Nakagawa Y, Kawakami R, Nakanishi M, Yasuno S, Usami S,Yoshimura A,Nakao K (2005) Hypertrophic responses to cardiotrophin- 1 are not mediated by STAT3, but via a MEK5-ERK5 pathway in cultured cardiomyocytes. J Mol Cell Cardiol 38:185–192

    PubMed  CAS  Google Scholar 

  135. Takeda K,Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T, Akira S (1997) Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality.Proc Natl Acad Sci USA 94:3801–3804

    PubMed  CAS  Google Scholar 

  136. Takimoto Y, Aoyama T, Iwanaga Y, Izumi T, Kihara Y, Pennica D, Sasayama S (2002) Increased expression of cardiotrophin-1 during ventricular remodeling in hypertensive rats. Am J Physiol Heart Circ Physiol 282:H896–901

    PubMed  CAS  Google Scholar 

  137. Talwar S, Squire IB, Downie PF, O’Brien RJ,Davies JE, Ng LL (2000) Elevated circulating cardiotrophin-1 in heart failure: relationship with parameters of left ventricular systolic dysfunction. Clin Sci (Lond) 99:83–88

    PubMed  CAS  Google Scholar 

  138. Tanaka T, Kanda T, McManus BM, Kanai H, Akiyama H, Sekiguchi K, Yokoyama T, Kurabayashi M (2001) Overexpression of interleukin-6 aggravates viral myocarditis: impaired increase in tumor necrosis factor-alpha. J Mol Cell Cardiol 33:1627–1635

    PubMed  CAS  Google Scholar 

  139. Tanimoto K, Saito Y, Hamanaka I, Kuwahara K, Harada M, Takahashi N, Kawakami R, Nakagawa Y, Nakanishi M, Adachi Y, Shirakami G, Fukuda K, Yoshimura A, Nakao K (2005) SOCS1/ JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide- induced left ventricular dysfunction in vivo. Circ J 69:1412–1417

    PubMed  CAS  Google Scholar 

  140. Tian ZJ,Cui W,Li YJ,Hao YM, Du J,Liu F, Zhang H, Zu XG, Liu SY, Chen L, An W (2004) Different contributions of STAT3,ERK1/2,and PI3-K signaling to cardiomyocyte hypertrophy by cardiotrophin- 1. Acta Pharmacol Sin 25:1157–1164

    PubMed  CAS  Google Scholar 

  141. Toh R,Kawashima S,Kawai M, Sakoda T, Ueyama T, Satomi-Kobayashi S, Hirayama S, Yokoyama M (2004) Transplantation of cardiotrophin-1- expressing myoblasts to the left ventricular wall alleviates the transition from compensatory hypertrophy to congestive heart failure in Dahl saltsensitive hypertensive rats. J Am Coll Cardiol 43:2337–2347

    PubMed  CAS  Google Scholar 

  142. Tone E, Kunisada K, Fujio Y, Matsui H, Negoro S, Oh H, Kishimoto T, Yamauchi-Takihara K (1998) Angiotensin II interferes with leukemia inhibitory factor-induced STAT3 activation in cardiac myocytes. Biochem Biophys Res Commun 253:147–150

    PubMed  CAS  Google Scholar 

  143. Tone E, Kunisada K, Kumanogoh A, Negoro S,Funamoto M,Osugi T,Kishimoto T, Yamauchi-Takihara K (2000) gp130-Dependent signalling pathway is not enhanced in gp130 transgenic heart after LIF stimulation. Cytokine 12:1512–1518

    PubMed  CAS  Google Scholar 

  144. Tonnessen T, Florholmen G, Henriksen UL, Christensen G (2003) Cardiopulmonary alterations in mRNA expression for interleukin-1beta, the interleukin-6 superfamily and CXCchemokines during development of postischaemic heart failure in the rat. Clin Physiol Funct Imaging 23:263–268

    PubMed  CAS  Google Scholar 

  145. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL (1996) Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 27:1201–1206

    PubMed  CAS  Google Scholar 

  146. Trial J, Rossen RD, Rubio J, Knowlton AA (2004) Inflammation and ischemia: macrophages activated by fibronectin fragments enhance the survival of injured cardiac myocytes. Exp Biol Med (Maywood) 229:538–545

    CAS  Google Scholar 

  147. Tsuruda T, Jougasaki M, Boerrigter G, Huntley BK, Chen HH, D’Assoro AB, Lee SC, Larsen AM, Cataliotti A, Burnett JC, Jr. (2002) Cardiotrophin-1 stimulation of cardiac fibroblast growth: roles for glycoprotein 130/ leukemia inhibitory factor receptor and the endothelin type A receptor. Circ Res 90:128–134

    PubMed  CAS  Google Scholar 

  148. Tsutamoto T, Hisanaga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabuchi N, Sawaki M, Kinoshita M (1998) Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 31:391–398

    PubMed  CAS  Google Scholar 

  149. Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Fujii M, Matsumoto T, Yamamoto T, Wang X, Asai S, Tsuji T, Tanaka H, Saito Y,Kuwahara K,Nakao K, Kinoshita M (2001) Relationship between plasma level of cardiotrophin- 1 and left ventricular mass index in patients with dilated cardiomyopathy. J Am Coll Cardiol 38:1485–1490

    PubMed  CAS  Google Scholar 

  150. Uozumi H,Hiroi Y, Zou Y,Takimoto E, Toko H,Niu P,Shimoyama M,Yazaki Y, Nagai R, Komuro I (2001) gp130 plays a critical role in pressure overload-induced cardiac hypertrophy. J Biol Chem 276:23115–23119

    PubMed  CAS  Google Scholar 

  151. Vasse M, Pourtau J, Trochon V, Muraine M,Vannier JP,Lu H, Soria J, Soria C (1999) Oncostatin M induces angiogenesis in vitro and in vivo. Arterioscler Thromb Vasc Biol 19:1835–1842

    PubMed  CAS  Google Scholar 

  152. Villegas S,Villarreal FJ, Dillmann WH (2000) Leukemia Inhibitory Factor and Interleukin-6 downregulate sarcoplasmic reticulum Ca2+ ATPase (SERCA2) in cardiac myocytes. Basic Res Cardiol 95:47–54

    PubMed  CAS  Google Scholar 

  153. Vona-Davis L, Zhu X, Yu AK, McFadden DW (2003) Modulation of interleukin- 6 in cardiac myoblasts during endotoxemia. J Surg Res 112:91–96

    PubMed  CAS  Google Scholar 

  154. Wang F, Seta Y, Baumgarten G, Engel DJ, Sivasubramanian N, Mann DL (2001) Functional significance of hemodynamic overload-induced expression of leukemia-inhibitory factor in the adult mammalian heart. Circulation 103:1296–1302

    PubMed  CAS  Google Scholar 

  155. Wang F, Trial J, Diwan A, Gao F, Birdsall H, Entman M,Hornsby P, Sivasubramaniam N, Mann D (2002) Regulation of cardiac fibroblast cellular function by leukemia inhibitory factor. J Mol Cell Cardiol 34:1309–1316

    PubMed  CAS  Google Scholar 

  156. Wang M,Markel T, Crisostomo P,Herring C, Meldrum KK, Lillemoe KD, Meldrum DR (2007) Deficiency of TNFR1 protects myocardium through SOCS3 and IL-6, but not p38 MAPK or IL-1 beta. Am J Physiol Heart Circ Physiol 292(4):H1694–H1699

    PubMed  CAS  Google Scholar 

  157. Watters DJ,Hendry IA (1987) Purification of a ciliary neurotrophic factor from bovine heart. J Neurochem 49:705–713

    PubMed  CAS  Google Scholar 

  158. Weiss TW, Kvakan H, Kaun C, Zorn G, Speidl WS, Pfaffenberger S,Maurer G, Huber K, Wojta J (2005) The gp130 ligand oncostatin M regulates tissue inhibitor of metalloproteinases-1 through ERK1/2 and p38 in human adult cardiac myocytes and in human adult cardiac fibroblasts: a possible role for the gp130/gp130 ligand system in the modulation of extracellular matrix degradation in the human heart. J Mol Cell Cardiol 39:545–551

    PubMed  CAS  Google Scholar 

  159. Weiss TW, Speidl WS,Kaun C, Rega G, Springer C, Macfelda K, Losert UM, Grant SL, Marro ML, Rhodes AD, Fuernkranz A, Bialy J, Ullrich R,Holzmann P, Pacher R,Maurer G,Huber K, Wojta J (2003) Glycoprotein 130 ligand oncostatin-M induces expression of vascular endothelial growth factor in human adult cardiac myocytes. Cardiovasc Res 59:628–638

    PubMed  CAS  Google Scholar 

  160. Wijelath ES, Carlsen B, Cole T, Chen J, Kothari S, Hammond WP (1997) Oncostatin M induces basic fibroblast growth factor expression in endothelial cells and promotes endothelial cell proliferation, migration and spindle morphology. J Cell Sci 110(Pt 7):871–879

    PubMed  CAS  Google Scholar 

  161. Wollert KC, Chien KR (1997) Cardiotrophin- 1 and the role of gp130-dependent signaling pathways in cardiac growth and development. J Mol Med 75:492–501

    PubMed  CAS  Google Scholar 

  162. Wollert KC,Drexler H (2001) The role of interleukin-6 in the failing heart. Heart Fail Rev 6:95–103

    PubMed  CAS  Google Scholar 

  163. Wollert KC, Taga T, Saito M, Narazaki M, Kishimoto T, Glembotski CC, Vernallis AB, Heath JK, Pennica D,Wood WI, Chien KR (1996) Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gp130/ leukemia inhibitory factor receptordependent pathways. J Biol Chem 271:9535–9545

    PubMed  CAS  Google Scholar 

  164. Xu J, Ren JF,Mugelli A, Belardinelli L, Keith Jr JC, Jr., Pelleg A (2002) Age-dependent atrial remodeling induced by recombinant human interleukin-11: implications for atrial flutter/fibrillation. J Cardiovasc Pharmacol 39: 435–440

    PubMed  CAS  Google Scholar 

  165. Yajima T, Yasukawa H, Jeon ES, Xiong D, Dorner A, Iwatate M, Nara M, Zhou H, Summers-Torres D, Hoshijima M, Chien KR,Yoshimura A,Knowlton KU (2006) Innate defense mechanism against virus infection within the cardiac myocyte requiring gp130-STAT3 signaling. Circulation 114:2364–2373

    PubMed  CAS  Google Scholar 

  166. Yamauchi-Takihara K, Kishimoto T (2000) Cytokines and their receptors in cardiovascular diseases–role of gp130 signalling pathway in cardiac myocyte growth and maintenance. Int J Exp Pathol 81:1–16

    PubMed  CAS  Google Scholar 

  167. Yamaura G, Turoczi T, Yamamoto F, Siddqui MA,Maulik N, Das DK (2003) STAT signaling in ischemic heart: a role of STAT5A in ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H476–482

    PubMed  CAS  Google Scholar 

  168. Yasukawa H,Hoshijima M,Gu Y,Nakamura T, Pradervand S, Hanada T, Hanakawa Y, Yoshimura A, Ross J, Jr., Chien KR (2001) Suppressor of cytokine signaling-3 is a biomechanical stress-inducible gene that suppresses gp130-mediated cardiac myocyte hypertrophy and survival pathways. J Clin Invest 108:1459–1467

    PubMed  CAS  Google Scholar 

  169. Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN,Yoshimura A (1999) The JAKbinding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. Embo J 18:1309–1320

    PubMed  CAS  Google Scholar 

  170. Yasukawa H, Ohishi M, Mori H, Murakami M, Chinen T,Aki D,Hanada T, Takeda K, Akira S, Hoshijima M, Hirano T, Chien KR,Yoshimura A (2003) IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages.Nat Immunol 4:551–556

    PubMed  CAS  Google Scholar 

  171. Yellon DM, Baxter GF (1999) Reperfusion injury revisited: is there a role for growth factor signaling in limiting lethal reperfusion injury? Trends Cardiovasc Med 9:245–249

    PubMed  CAS  Google Scholar 

  172. Yoshida K, Taga T, Saito M, Suematsu S, Kumanogoh A, Tanaka T, Fujiwara H,Hirata M,Yamagami T,Nakahata T, et al. (1996) Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. Proc Natl Acad Sci USA 93:407–411

    PubMed  CAS  Google Scholar 

  173. Zhang X, Guo A, Yu J, Possemato A, Chen Y, Zheng W, Polakiewicz RD, Kinzler KW, Vogelstein B, Velculescu VE, John Wang Z (2007) Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T. Proc Natl Acad Sci USA 104:4060–4064

    PubMed  CAS  Google Scholar 

  174. Zolk O, Engmann S,Munzel F, Krajcik R (2005) Chronic cardiotrophin-1 stimulation impairs contractile function in reconstituted heart tissue. Am J Physiol Endocrinol Metab 288:E1214–1221

    PubMed  CAS  Google Scholar 

  175. Zolk O, Ng LL, O’Brien RJ,Weyand M, Eschenhagen T (2002) Augmented expression of cardiotrophin-1 in failing human hearts is accompanied by diminished glycoprotein 130 receptor protein abundance. Circulation 106:1442–1446

    PubMed  CAS  Google Scholar 

  176. Zou Y, Takano H, Mizukami M, Akazawa H, Qin Y, Toko H, Sakamoto M, Minamino T, Nagai T, Komuro I (2003) Leukemia inhibitory factor enhances survival of cardiomyocytes and induces regeneration of myocardium after myocardial infarction. Circulation 108:748–753

    PubMed  CAS  Google Scholar 

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  1. Dept. of Cardiology & Angiology, Medical School Hannover, Hannover, Germany

    P. Fischer & D. Hilfiker-Kleiner PhD

  2. Abt.Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg Straße 1, 30625, Hannover, Germany

    D. Hilfiker-Kleiner PhD

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Fischer, P., Hilfiker-Kleiner, D. Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis. Basic Res Cardiol 102, 279–297 (2007). https://doi.org/10.1007/s00395-007-0658-z

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