Volume 84, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Chagas cardiomyopathy remodeling is based on the presence of in heart tissue and on the complex inflammatory response leading to a myocardium fibrosis and alterations in conductive and functional heart parameters. This study aims to evaluate Simvastatin on the inflammatory response and heart functionality using dogs infected with Y strain of . Animals were treated daily with Simvastatin (20 mg) for 6 months and submitted to clinical and immunopathological evaluations. Simvastatin reduced heart expression and serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) but not interleukin-10 (IL-10), possibly favoring blood parasitism but reducing inflammation and fibrosis in the left ventricle and right atrium. Simvastatin also ameliorated ejection fraction, diastolic diameter, and mass index of the left ventricle 6 months after infection. This study suggests that more investigation should be performed on the use of statins as a prophylactic therapy against cardiac remodeling because of their effects on modifying immune response and benefiting functional parameters in dogs with -induced ventricular dysfunctions.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Pan American Health Organization (PAHO)–World Health Organization (WHO), 2006. Estimacion cuantitativa de la enfermedad de Chagas en las Americas. Montevideo, Uruguay: Organizacion Panamericana de la Salud; CD/425-06. [Google Scholar]
  2. Feldman AM, McNemara D, , 2000. Myocarditis. N Engl J Med 343: 13881398.[Crossref] [Google Scholar]
  3. Rocha MO, Teixeira MM, Ribeiro AL, , 2007. An update on the management of Chagas cardiomyopathy. Expert Rev Anti Infect Ther 5: 727743.[Crossref] [Google Scholar]
  4. Dutra WO, Rocha MO, Teixeira MM, , 2005. The clinical immunology of human Chagas disease. Trends Parasitol 21: 581587.[Crossref] [Google Scholar]
  5. Gutierrez FR, Guedes PM, Gazzinelli RT, Silva JS, , 2009. The role of parasite persistence in pathogenesis of Chagas heart disease. Parasite Immunol 31: 673685.[Crossref] [Google Scholar]
  6. Abrahamsohn IA, Coffman RL, , 1996. Trypanosoma cruzi: IL-10, TNF, IFN-gamma and IL-12 regulate innate and acquired immunity to infection. Exp Parasitol 84: 231244.[Crossref] [Google Scholar]
  7. Brener Z, Gazzinelli RT, , 1997. Immunological control of Trypanosoma cruzi infection and pathogenesis of Chagas disease. Int Arch Allergy Immunol 114: 103110.[Crossref] [Google Scholar]
  8. Talvani A, Ribeiro CS, Aliberti JC, Michailowsky V, Santos PV, Murta SM, Romanha AJ, Almeida IC, Farber J, Lannes-Vieira J, Silva JS, Gazzinelli RT, , 2000. Kinetics of cytokine gene expression in experimental chagasic cardiomyopathy: tissue parasitism and endogenous IFN-gamma as important determinants of chemokine mRNA expression during infection with Trypanosoma cruzi . Microbes Infect 2: 851866.[Crossref] [Google Scholar]
  9. Urbina JA, , 2009. New advances in the management of a long-neglected disease. Clin Infect Dis 49: 16851687.[Crossref] [Google Scholar]
  10. Node K, Fujita M, Kitakaze M, Hori M, Liao JK, , 2003. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 108: 839843.[Crossref] [Google Scholar]
  11. Shanes JG, Minadeo KN, Moret A, Groner M, Tabaic SA, , 2007. Statin therapy in heart failure: prognostic effects and potential mechanisms. Am Heart J 154: 617623.[Crossref] [Google Scholar]
  12. Weis M, Heeschen C, Glassford AJ, Cooke JP, , 2002. Statins have biphasic effects on angiogenesis. Circulation 105: 739745.[Crossref] [Google Scholar]
  13. Cheng X, Liao YH, Zhang J, Li B, Ge H, Yuan J, Wang M, Lu B, Liu Y, Cheng Y, , 2005. Effects of Atorvastatin on Th polarization in patients with acute myocardial infarction. Eur J Heart Fail 7: 10991104.[Crossref] [Google Scholar]
  14. Robinson JG, , 2008. Models for describing relations among the various statin drugs, low-density lipoprotein cholesterol lowering, pleiotropic effects and cardiovascular risk. Am J Cardiol 101: 10091015.[Crossref] [Google Scholar]
  15. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN, , 2004. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 291: 10711080.[Crossref] [Google Scholar]
  16. Mancini GB, Etminan M, Zhang B, Levesque LE, FitzGerald JM, Brophy JM, , 2006. Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol 47: 25542560.[Crossref] [Google Scholar]
  17. Guedes PM, Veloso VM, Afonso LC, Caliari MV, Carneiro CM, Diniz LF, Marques-da-Silva EA, Caldas IS, Do Valle Matta MA, Souza SM, Lana M, Chiari E, Galvão LM, Bahia MT, , 2009. Development of chronic cardiomyopathy in canine Chagas disease correlates with high IFN-gamma, TNF-alpha, and low IL-10 production during the acute infection phase. Vet Immunol Immunopathol 130: 4352.[Crossref] [Google Scholar]
  18. Guedes PM, Veloso VM, Talvani A, Diniz LF, Caldas IS, Do-Valle-Matta MA, Santiago-Silva J, Chiari E, Galvão LM, Silva JS, Bahia MT, , 2010. Increased type 1 chemokine expression in experimental Chagas disease correlates with cardiac pathology in Beagle dogs. Vet Immunol Immunopathol 138: 106113.[Crossref] [Google Scholar]
  19. Zaca V, Rastogi S, Imai M, Wang M, Sharov VG, Jiang A, Goldstein S, Sabbah HN, , 2007. Chronic monotherapy with Rosuvastatin prevents progressive left ventricular dysfunction and remodeling in dogs with heart failure. J Am Coll Cardiol 50: 551557.[Crossref] [Google Scholar]
  20. Shiroshita-Takeshita A, Brundel BJJM, Burstein B, Leung TK, Mitamura H, Ogawa S, Nattel S, , 2007. Effects of simvastatin on the development of the atrial fibrillation substrate in dogs with congestive heart failure. Cardiovasc Res 74: 7584.[Crossref] [Google Scholar]
  21. Pedersen TR, Tobert JA, , 2004. Simvastatin: a review. Expert Opin Pharmacother 5: 25832596.[Crossref] [Google Scholar]
  22. Morris SA, Tanowitz HB, Wittner M, Bilezikian JP, , 1990. Pathophysiological insights into the cardiomyopathy of Chagas disease. Circulation 82: 19001909.[Crossref] [Google Scholar]
  23. Botoni FA, Poole-Wilson PA, Ribeiro AL, Okonko DO, Oliveira BM, Pinto AS, Teixeira MM, Teixeira AL, Jr Reis AM, Dantas JB, Ferreira CS, Tavares WC, Jr Rocha MO, , 2007. A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy. Am Heart J 153: 544e1544e8.[Crossref] [Google Scholar]
  24. Bestetti RB, Theodoropoulos TA, Cardinalli-Neto A, , 2007. Treating patients with Chagas cardiomyopathy with chronic heart failure in the contemporary era. Am Heart J 154: 35e.[Crossref] [Google Scholar]
  25. Issa VS, Amaral AF, Cruz FD, Ferreira SM, Guimarães GV, Chizzola PR, Souza GE, Bacal F, Bocchi EA, , 2010. Beta-Blocker therapy and mortality of patients with Chagas cardiomyopathy: a subanalysis of the REMADHE prospective Trial. Circ Heart Fail 3: 8288.[Crossref] [Google Scholar]
  26. Paula-Costa G GP, Silva RR, Pedrosa MC, Pinho V, Lima WG, Teixeira MM, Bahia MT, Talvani A, , 2010. Enalapril prevents cardiac immune-mediated damage and exerts anti-Trypanosoma cruzi activity during acute phase of experimental Chagas disease. Parasite Immunol 32: 202208.[Crossref] [Google Scholar]
  27. Goldstein JL, Brown MS, , 1990. Regulation of the mevalonate pathway. Nature 343: 425430.[Crossref] [Google Scholar]
  28. Concepcion JL, Gonzalez-Pacanowska D, Urbina JA, , 1998. 3-Hydroxy-3-methyl-glutaryl-CoA reductase in Trypanosoma (Schizotrypanum) cruzi: subcellular localization and kinetic properties. Arch Biochem Biophys 352: 114120.[Crossref] [Google Scholar]
  29. Silva JS, Machado FS, Martins GA, , 2003. The role of nitric oxide in the pathogenesis of Chagas disease. Front Biosci 1: 314325.[Crossref] [Google Scholar]
  30. Cummings KL, Tarleton RL, , 2004. Inducible nitric oxide synthase is not essential for control of Trypanosoma cruzi infection in mice. Infect Immun 72: 40814089.[Crossref] [Google Scholar]
  31. Coelho PS, Klein A, Talvani A, Coutinho SF, Takeuchi O, Akira S, Silva JS, Canizzaro H, Gazzinelli RT, Teixeira MM, , 2002. Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes induce in vivo leukocyte recruitment dependent on MCP-1 production by IFN-gamma-primed-macrophages. J Leukoc Biol 71: 837844. [Google Scholar]
  32. Gomes JA, Bahia-Oliveira LM, Rocha MO, Martins-Filho OA, Gazzinelli G, Correa-Oliveira R, , 2003. Evidence that development of severe cardiomyopathy in human Chagas' disease is due to a Th1-specific immune response. Infect Immun 71: 11851193.[Crossref] [Google Scholar]
  33. Cunha-Neto E, Nogueira LG, Teixeira PC, Ramasawmy R, Drigo SA, Goldberg AC, Fonseca SG, Bilate AM, Kalil J, , 2009. Immunological and non-immunological effects of cytokines and chemokines in the pathogenesis of chronic Chagas disease cardiomyopathy. Mem Inst Oswaldo Cruz 104 (Suppl 1): 252258.[Crossref] [Google Scholar]
  34. de Lana M, Chiari E, Tafuri WL, , 1992. Experimental Chagas' disease in dogs. Mem Inst Oswaldo Cruz 87: 5971.[Crossref] [Google Scholar]
  35. Gunja-Smith Z, Morales AR, Romanelli R, Woessner FR, Jr, 1996. Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline crosslinks. Am J Pathol 1448: 16391648. [Google Scholar]
  36. Chou DH, Lee W, McCulloch CA, , 1996. TNF-alpha inactivation of collagen receptors: implications for fibroblasts function and fibrosis. J Immunol 156: 43544362. [Google Scholar]
  37. Gurantz D, Cowling RT, Villarreal FJ, Greenberg BH, , 1999. Tumor necrosis factor-alpha upregulates angiotensin II type 1 receptors on cardiac fibroblasts. Circ Res 85: 272279.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 12 Aug 2010
  • Accepted : 01 Nov 2010
  • Published online : 04 Feb 2011

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error