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Changes in cellular contractility and cytokines profile during Trypanosoma cruzi infection in mice

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Abstract

Trypanosoma cruzi, an intracellular protozoan parasite infecting a wide variety of vertebrates, is the agent responsible for Chagas’ disease. This pathology often results in severe inflammatory heart condition and it is one of the major causes of dilated cardiomyopathy leading to heart failure in Latin America. Nevertheless, little is known about the changes in isolate cardiac myocytes contractility during the development of this pathology. Here we report a relationship between cytokines profile of mice infected with T. cruzi and the modifications in the cellular contractility pattern. We found that cellular contractility, measured as fractional shortening, showed a complex behavior. The changes were evaluated during the acute phase (15, 30 and 45 dpi) and chronic phase (>90 dpi). The time to half contraction and relaxation were lengthier despite the number of days after infection or the heart region evaluated. The maximal contraction and relaxation velocities were significantly slower. The observed changes in cellular contractility were correlated with the presence of circulating IFN-γ, TNF-α and MCP-1/CCL2 during the course of infection. Together, our data demonstrate that cellular contractility is altered in the three heart regions studied, and these alterations are observed at the very beginning of the parasitism and they remained until the chronic phase has been reached. Indeed, we propose a role for IFN-γ, TNF-α and MCP-1/CCL2 in the mechanical heart remodeling during experimental Chagas’ disease.

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References

  1. Amadou A, Nawrocki A, Best-Belpomme M, Pavoine C, Pecker F (2002) Arachidonic acid mediates dual effect of TNF-alpha on Ca2+ transients and contraction of adult rat cardiomyocytes. Am J Physiol Cell Physiol 282:C1339–C1347

    PubMed  CAS  Google Scholar 

  2. Andrade ZA (1999) Immunopathology of Chagas’ disease. Mem Inst Oswaldo Cruz 94:71–80

    PubMed  Google Scholar 

  3. Avila G, Medina IM, Jimenez E, Elizondo G, Aguilar CI (2007) Transforming growth factor-1 decreases cardiac muscle L-type Ca2+ current and charge movement by acting on the Cav1.2 mRNA. Am J Physiol Heart Circ Physiol 292:H622–H633

    Article  PubMed  CAS  Google Scholar 

  4. Bestetti RB, Rossi MA (1997) A rationale approach for mortality risk stratification in Chagas’ heart disease. Int J Cardiol 58:199–209

    Article  PubMed  CAS  Google Scholar 

  5. Borda ES, Sterin-Borda L (1996) Antiadrenergic and muscarinic receptor antibodies in Chagas’ cardiomyopathy. Int J Cardiol 54:149–156

    Article  PubMed  CAS  Google Scholar 

  6. Brener Z (1962) Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi. Rev Inst Med Trop 4:389–396

    CAS  Google Scholar 

  7. Control of Chagas’ disease: Second Report of the WHO Expert Committee. Geneva, Switzerland: World Health Organization; (2002) Technical report series 905

  8. Damas JK, Aukrust P, Ueland T, Odegaard A, Eiken HG, Gullestad L, Sejersted OM, Christensen G (2001) Monocyte chemoattractant protein-1 enhances and interleukin-10 suppresses the production of inflammatory cytokines in adult rat cardiomyocytes. Basic Res Cardiol 96:345–352

    Article  PubMed  CAS  Google Scholar 

  9. Dewald O, Zymek P, Winkelmann K, Koerting A, Ren G, Abou-Khamis T, Michael LH, Rollins BJ, Entman ML, Frangogiannis NG (2005) CCL2/monocyte chemoattractant protein-1 regulates inflammatory responses critical to healing myocardial infarcts. Circ Res 96:881–889

    Article  PubMed  CAS  Google Scholar 

  10. dos Santos PV, Roffe E, Santiago HC, Torres RA, Marino AP, Paiva CN, Silva AA, Gazzinelli RT, Lannes-Vieira J (2001) Prevalence of CD8(+)alpha beta T cells in Trypanosoma cruzi-elicited myocarditis is associated with acquisition of CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype and expression of IFN-gamma-inducible adhesion and chemoattractant molecules. Microb Infect 3:971–984

    Article  CAS  Google Scholar 

  11. Duncan DJ, Hopkins PM, Harrison SM (2007) Negative inotropic effects of tumour necrosis factor-alpha and interleukin-1beta are ameliorated by alfentanil in rat ventricular myocytes. Br J Pharmacol 150:720–726

    Article  PubMed  CAS  Google Scholar 

  12. Egman DM, Leon JS (2002) Pathogenesis of Chagas’ heart disease: role of autoimmunity. Acta Trop 81:123–132

    Article  Google Scholar 

  13. Fernandez-Culasso A, Pagline-Olivia P, Palma JÁ, Lacuara JL (1991) Isometric developed tension and histopathology of myocardium of chagasic mice: part 1. APPTLA 41:397–404

    PubMed  CAS  Google Scholar 

  14. Fernandez-Velasco M, Ruiz-Hurtado G, Hurtado O, Moro MA, Delgado C (2007) TNF-alpha downregulates transient outward potassium current in rat ventricular myocytes through iNOS overexpression and oxidant species generation. Am J Physiol Heart Circ Physiol 293:H238–H245

    Article  PubMed  CAS  Google Scholar 

  15. Frederici EE, Albemann WH, Neva FA (1964) Chronic and progressive myocarditis and myositis in C3H Mice infected with Trypanosoma cruzi. Am J Trop Med Hyg 13:272–280

    Google Scholar 

  16. Fuse K, Kodama M, Hanawa H, Okura Y, Ito M, Shiono T, Maruyama S, Horino S, Kato K, Watanabe K, Aizawa Y (2001) Enhanced expression and production of monocyte chemoattractant protein-1 in myocarditis. Clin Exp Immunol 124:346–352

    Article  PubMed  CAS  Google Scholar 

  17. Goldhaber JI, Kim KH, Natterson PD, Lawrence T, Yang P, Weiss JN (1996) Effects of TNF-alpha on [Ca2+] i and contractility in isolated adult rabbit ventricular myocytes. Am J Physiol Heart Circ Physiol 271:H1449–H1455

    CAS  Google Scholar 

  18. Goser S, Ottl R, Brodner A, Dengler TJ, Torzewski J, Egashira K, Rose NR, Katus HA, Kaya Z (2005) Critical role for monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha in induction of experimental autoimmune myocarditis and effective anti-monocyte chemoattractant protein-1 gene therapy. Circulation 112:3400–3407

    Article  PubMed  Google Scholar 

  19. Heinele J, Kempt T, Kraft T, Hilfiker A, Morawietz H, Scheubel RJ, Caroni P, Lohmann SM, Drexler H, Wollert KC (2003) Downregulation of cytoskeletal muscle LIM protein by nitric oxide: impact on cardiac myocyte hypertrophy. Circulation 107:1424–1432

    Article  Google Scholar 

  20. Janczewski AM, Kadokami T, Lemster B, Frye CS, McTiernan CF, Feldman AM (2003) Morphological and functional changes in cardiac myocytes isolated from mice overexpressing TNF-alpha. Am J Physiol Heart Circ Physiol 284:H960–H969

    PubMed  CAS  Google Scholar 

  21. Kolattukudy PE, Quach T, Bergese S, Breckenridge S, Hensley J, Altschuld R, Gordillo G, Klenotic S, Orosz C, Parker-Thornburg J (1998) Myocarditis induced by targeted expression of the MCP-1 gene in murine cardiac muscle. Am J Pathol 152:101–111

    PubMed  CAS  Google Scholar 

  22. Krown KA, Yasui K, Brooker MJ, Dubin AE, Nguyen C, Harris GL, McDonough PM, Glembotski CC, Palade PT, SAbbadini RA (1995) TNF alpha receptor expression in rat cardiac myocytes: TNF alpha inhibition of L-type Ca2+ current and Ca2+ transients. FEBS Lett 376:24–30

    Article  PubMed  CAS  Google Scholar 

  23. Labovsky V, Smulski CR, Gómez K, Levy G, Levin MJ (2007) Anti-beta1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease. Clin Exp Immunol 148:440–449

    PubMed  CAS  Google Scholar 

  24. Lauton-Santos S, Guatimosin S, Castro CH, Oliveira FA, Almeida AP, Dias-Peixoto MF, Gomes MA, Pessoa P, Pesquero JL, Bader M, Cruz JS (2007) Kinin B1 receptos participates in the control of cardiac function in mice. Life Sci 81:814–822

    Article  PubMed  CAS  Google Scholar 

  25. Liu SJ, Zhou W, Kennedy R (1999) Suppression of b-adrenergic responsiveness of L-type Ca21 current by IL-1b in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 276:141–148

    Google Scholar 

  26. Lopez-Bergami P, Scaglione J, Levin MJ (2001) Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic. FASEB J 15:2602–2612

    Article  PubMed  CAS  Google Scholar 

  27. Machado FS, Martins GA, Aliberti JC, Mestriner FL, Cunha FQ, Silva JS (2000) Trypanosoma cruzi-infected cardiomyocytes produce chemokines and cytokines that trigger potent nitric oxide-dependent trypanocidal activity. Circulation 102:3003–3008

    PubMed  CAS  Google Scholar 

  28. Machado FS, Souto JT, Rossi MA, Esper L, Tanowitz HB, Aliberti J, Silva JS (2008) Nitric oxide sinthase 2 modulates chemokine production by Trypanosoma cruzi infected cardiac myocyte. Microb Infect. doi:10.1016/j.micinf.2008.09.009

  29. Medina FA, Cohen AW, de Almeida CJ, Nagajyothi F, Braunstein VL, Teixeira MM, Tanowitz HB, Lisanti MP (2007) Immune dysfunction in caveolin-1 null mice following infection with Trypanosoma cruzi (Tulahuen strain). Microb Infect 9:325–333

    Article  CAS  Google Scholar 

  30. Morimoto H, Hirose M, Takahashi M, Kawaguchi M, Ise H, Kolattukudy PE, Yamada M, Ikeda U (2008) MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of reactive oxygen species. Cardiovasc Res 78:554–562

    Article  PubMed  CAS  Google Scholar 

  31. Muller-Werdan U, Engelmann H, Werdan K (1998) Cardiodepression by tumor necrosis factor-alpha. Eur Cytokine Netw 9:689–691

    PubMed  CAS  Google Scholar 

  32. Nair RR, Nair P (2001) Age-dependent variation in contractility of adult cardiac myocytes. Int J Biochem Cell Biol 32:119–125

    Article  Google Scholar 

  33. Natali AJ, Turner DL, Harrison SM, Wire E (2001) Regional effects of voluntary exercise on cell size and contraction-frequency responses in rat cardiac myocyte. J Exp Biol 204:1191–1199

    PubMed  CAS  Google Scholar 

  34. Nerbonne JM, Kass RS (2005) Molecular physiology of cardiac repolarization. Physiol Rev 85:1205–1253

    Article  PubMed  CAS  Google Scholar 

  35. Sheddon M, Shah AM, Casadei B (2007) Cardiomyocyte as effectors of nitric oxide signalling. Cardiovasc Res 75:315–326

    Article  Google Scholar 

  36. Silva JS, Vespa GN, Cardoso MA, Aliberti JC, Cunha FQ (1995) Tumor necrosis factor alpha mediates resistance to Trypanosoma cruzi infection in mice by inducing nitric oxide production in infected gamma interferon-activated macrophages. Infect Immun 63:4862–4867

    PubMed  CAS  Google Scholar 

  37. Skyschally A, Gres P, Hoffmann S, Haude M, Erbel R, Schulz R, Heusch G (2007) Bidirectional role of tumor necrosis factor-α in coronary microembolization. Circ Res 100:140–146

    Article  PubMed  CAS  Google Scholar 

  38. Tarleton RL (2001) Parasite persistence in the aetiology of Chagas’ disease. Int J Parasitol 31:550–554

    Article  PubMed  CAS  Google Scholar 

  39. Tarleton RL (2007) Immune system recognition of Trypanosoma cruzi. Curr Opin Immunol 19:430–434

    Article  PubMed  CAS  Google Scholar 

  40. Teixeira AR, Teixeira ML, Santos-Buch CA (1975) The immunology of experimental Chagas’ disease. IV: production of lesions in rabbits similar to those of chronic Chagas’ disease in man. Am J Pathol 80:163–180

    PubMed  CAS  Google Scholar 

  41. Teixeira MM, Gazzinelli RT, Silva JS (2002) Chemokines, inflammation and Trypanosoma cruzi infection. Trends Parasitol 18:262–265

    Article  PubMed  CAS  Google Scholar 

  42. Thielmann M, Dorge H, Martin C, Belosjorow S, Schwanke U, de Sand AV, Konietzka I, Buchert A, Kruger A, Schulz R, Heusch G (2002) Myocardial dysfunction with coronary microembolization. Circ Res 90:807–813

    Article  PubMed  CAS  Google Scholar 

  43. Wen JJ, Vyatkina G, Garg N (2004) Oxidative damage during chagasic cardiomyopathy development: role of mitochondrial oxidant release and inefficient antioxidant defense. Free Radic Biol Med 37:1821–1833

    Article  PubMed  CAS  Google Scholar 

  44. Wen JJ, Yachelini PC, Sembaj A, Manzur RE, Garg NJ (2006) Increased oxidative stress is correlated with mitochondrial dysfunction in chagasic patients. Free Radic Biol Med 41:270–276

    Article  PubMed  CAS  Google Scholar 

  45. Yndestad A, Damas JK, Oie E, Ueland T, Gullestad L, Aukrust P (2007) Role of inflammation in the progression of heart failure. Curr Cardiol Rep 9:236–241

    Article  PubMed  Google Scholar 

  46. Zhang C (2008) The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol 103:398–406

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Fapemig, CNPq and CAPES.

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Correspondence to Jader S. Cruz.

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D. Roman-Campos and H.L.L. Duarte contributed equally.

Returned for 1. Revision: 19 November 2008 1. Revision received: 25 November 2008

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Roman-Campos, D., Duarte, H.L.L., Sales, P.A. et al. Changes in cellular contractility and cytokines profile during Trypanosoma cruzi infection in mice. Basic Res Cardiol 104, 238–246 (2009). https://doi.org/10.1007/s00395-009-0776-x

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  • DOI: https://doi.org/10.1007/s00395-009-0776-x

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