• 1.

    Pérez-Molina JA, Molina I, 2018. Chagas disease. Lancet 391: 8294.

  • 2.

    Umezawa ES, Stolf AM, Corbett CE, Shikanai-Yasuda MA, 2001. Chagas’ disease. Lancet 357: 797799.

  • 3.

    Oliveira-Filho J et al., 2005. Chagas disease is an independent risk factor for stroke: baseline characteristics of a Chagas disease cohort. Stroke 36: 20152017.

    • Search Google Scholar
    • Export Citation
  • 4.

    Jin R, Liu L, Zhang S, Nanda A, Li G, 2013. Role of inflammation and its mediators in acute ischemic stroke. J Cardiovasc Transl Res 6: 834851.

  • 5.

    Jander S, Sitzer M, Schumann R, Schroeter M, Siebler M, Steinmetz H, Stoll G, 1998. Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization. Stroke 29: 16251630.

    • Search Google Scholar
    • Export Citation
  • 6.

    Mattila KJ, Valtonen VV, Nieminen MS, Asikainen S, 1998. Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke. Clin Infect Dis 26: 719734.

    • Search Google Scholar
    • Export Citation
  • 7.

    Elkind MS, Lin IF, Grayston JT, Sacco RL, 2000. Chlamydia pneumoniae and the risk of first ischemic stroke. The Northern Manhattan Stroke Study. Stroke 31: 15211525.

    • Search Google Scholar
    • Export Citation
  • 8.

    Jefferson AL et al., 2007. Inflammatory biomarkers are associated with total brain volume. The Framingham Heart Study Neurology 68: 10321038.

  • 9.

    Jones WJ et al., 2001. Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by neurological history and examination. Stroke 32: 22322236.

    • Search Google Scholar
    • Export Citation
  • 10.

    Milting H et al., 2008. Plasma biomarkers of myocardial fibrosis and remodeling in terminal heart failure patients supported by mechanical circulatory support devices. J Heart Lung Transplant 27: 589596.

    • Search Google Scholar
    • Export Citation
  • 11.

    Batlle M, Pérez-Villa F, García-Pras E, Lázaro A, Orús J, Roqué M, Roig E, 2007. Down-regulation of matrix metalloproteinase-9 (MMP-9) expression in the myocardium of congestive heart failure patients. Transplant Proc 39: 23442346.

    • Search Google Scholar
    • Export Citation
  • 12.

    Polyakova V, Loeffler I, Hein S, Miyagawa S, Piotrowska I, Dammer S, Risteli J, Schaper J, Kostin S, 2011. Fibrosis in endstage human heart failure: severe changes in collagen metabolism and MMP/TIMP profiles. Int J Cardiol 151: 1833.

    • Search Google Scholar
    • Export Citation
  • 13.

    Takawale A, Zhang P, Patel VB, Wang X, Oudit G, Kassiri Z, 2017. Tissue inhibitor of matrix metalloproteinase-1 promotes myocardial fibrosis by mediating CD63-integrin β1 interaction Hypertension69: 10921103.

  • 14.

    McMurray JJV et al., 2014. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371: 9931004.

  • 15.

    Radosinska J, Barancik M, Norbert Vrbjar N, 2017. Heart failure and role of circulating MMP-2 and MMP-9. Panminerva Med 59: 241253.

  • 16.

    Medeiros NI, Gomes JAS, Correa-Oliveira R, 2017. Synergic and antagonistic relationship between MMP-2 and MMP-9 with fibrosis and inflammation in Chagas’ cardiomyopathy. Parasite Immunol 39 :.

    • Search Google Scholar
    • Export Citation
  • 17.

    Kaplan P, Vrtovec B, Jug B, 2016. Orosomucoid is an independent predictor of prognosis in chronic heart failure. Wien Klin Wochenschr 128: 870874.

    • Search Google Scholar
    • Export Citation
  • 18.

    Neri LR et al., 2019. Factors associated with abnormal cardiac magnetic resonance imaging in embolic stroke of undetermined source. Int J Stroke 14: NP6NP9.

    • Search Google Scholar
    • Export Citation
  • 19.

    Lima-Costa MF et al., 2009. A population-based study of the association between Trypanosoma cruzi infection and cognitive impairment in old age (the Bambuí Study). Neuroepidemiology 32: 122128.

    • Search Google Scholar
    • Export Citation
  • 20.

    Lima-Costa MF, Matos DL, Ribeiro AL, 2010. Chagas disease predicts 10-year stroke mortality in community-dwelling elderly: the Bambuí cohort study of aging. Stroke 41: 24772482.

    • Search Google Scholar
    • Export Citation
  • 21.

    Dias JS, Lacerda AM, Vieira-de-Melo RM, Viana LC, Jesus PA, Reis FJ, Nitrin R, Fichaman HC, Lopes AA, Oliveira-Filho J, 2009. Cognitive dysfunction in chronic Chagas disease cardiomyopathy. Dement Neuropsychol 3: 2733.

    • Search Google Scholar
    • Export Citation
  • 22.

    Leon-Sarmiento FE et al., 2004. Trypanosoma cruzi-associated cerebrovascular disease: a case-control study in eastern Colombia. J Neurol Sci 217: 6164.

    • Search Google Scholar
    • Export Citation
  • 23.

    de Queiroz AC, Ramos EA, 1979. Anatomo-pathological study of the brain in idiopathic cardiomegaly. Arq Neuropsiquiatr 37: 405411.

  • 24.

    Oliveira-Filho J et al., 2009. Chagas disease is independently associated with brain atrophy. J Neurol 256: 13631365.

  • 25.

    Nunes MC, Barbosa MM, Ribeiro AL, Barbosa FB, Rocha MO, 2009. Ischemic cerebrovascular events in patients with Chagas cardiomyopathy: a prospective follow-up study. J Neurol Sci 278: 96101.

    • Search Google Scholar
    • Export Citation
  • 26.

    Nunes MC et al., 2015. Prevalence and risk factors of embolic cerebrovascular events associated with Chagas heart disease. Glob Heart 10: 151157.

    • Search Google Scholar
    • Export Citation
 
 
 

 

 
 
 

 

 

 

 

 

 

Tissue Inhibitor of Metalloproteinase-1 Is Increased in Chagasic Cardiomyopathy

View More View Less
  • 1 Postgraduate Program in Health Sciences, Federal University of Bahia, Salvador, Brazil;
  • | 2 Neurocardiology Research Group, Federal University of Bahia, Salvador, Brazil;
  • | 3 Cardiology Service, Federal University of Bahia, Salvador, Brazil;
  • | 4 Cardiology Service, Federal University of Minas Gerais, Belo Horizonte, Brazil;
  • | 5 Neurology Service, Brown University, Providence, Rhode Island

ABSTRACT.

Chagas disease (CD) mainly conveys stroke risk through structural cardiac disease. However, stroke and cognitive impairment are seen in CD independently of cardiac disease severity. Chronic inflammation may be an explanation for this association, because inflammation plays an important role in the pathogenesis of acute ischemic stroke and dementia. In the present study, we selected five candidate biomarkers for Chagas disease: interleukin-6, membrane metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP1), orosomucoid, and neprilysin. We sought to determine if mean levels of proinflammatory biomarkers are higher in patients with heart failure (HF) associated with Chagas disease when compared with other etiologies of HF. Patients were consecutively enrolled from subspecialty HF outpatient clinics at two university-based hospitals. Serum biomarker levels from blood samples were analyzed by ELISA. Severity of HF on echocardiography was worse in non-CD when compared with CD patients. No significant difference was observed in the levels of candidate biomarkers between the CD and non-CD groups. We found a significantly 2.2 ng/mL higher level of TIMP1 in CD when compared with non-CD patients with HF after adjustment for age and gender (95% confidence interval = 0.1 to 4.5, P = 0.037). In patients with heart failure, serum TIMP1 is increased in Chagas patients despite a lower myocardial disease severity on echocardiography when compared with non-Chagas patients. TIMP1 is probably one of multiple mediators of inflammatory injury.

    • Supplemental Materials (DOCX 49 KB)

Author Notes

Address correspondence to Jamary Oliveira-Filho, Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Largo do Terreiro de Jesus s/n, Centro Histórico, Salvador, Bahia, Brazil, 40026-010. E-mail: jamaryof@ufba.br

Financial support: This study was supported by NIH grant RO1NS064905.

Authors’ addresses: Karina Oliveira Garcia, Thiago Cerqueira Silva, and Jamary Oliveira-Filho, Postgraduate Program in Health Sciences and Neurocardiology Research Group, Federal University of Bahia, Bahia, Brazil, E-mails: kaolivegarcia@gmail.com, csilvathiago@hotmail.com, and jamary@mail.harvard.edu. Maria do Carmo Pereira Nunes, Lucas Campos Barbosa e Silva, and Antonio Luiz Pinho Ribeiro, Cardiology Service, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, Brazil, E-mails: mcarmo@waymail.com.br, lucascbs1103@hotmail.com, and alpr1963br@gmail.com. Iuri Ferreira Felix, Murilo Araujo Oliveira, Maria Eduarda Lisboa Marques, Leila Souza Brito Santos, Paulo Roberto Sampaio Peixoto Sousa, Pedro José Ramiro Muiños, Renata Martins Maia, Marília Bazzo Catto, Pedro Antonio Pereira Jesus, and Giovanna Ladeia Rocha, Neurocardiology Research Group, Federal University of Bahia, Salvador, Brazil, E-mails: iuri.felix.96@gmail.com, muriloaraujokaulegal@hotmail.com, duda_lisboa2011@hotmail.com, leila-briito@hotmail.com, prspdesousa@gmail.com, pedromuinos@hotmail.com, renata.martins.maia@hotmail.com, mariliacatto@hotmail.com, papj@terra.com.br, and giovannaladeia@gmail.com. Roque Aras, Cardiology Service, Federal University of Bahia, Salvador, Brazil, E-mail: raras@ufba.br. Karen L. Furie, Neurology Service, Brown University, Providence, RI, E-mail: kfurie@lifespan.org.

Save