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European Journal of Heart Failure Advance Access originally published online on August 4, 2009
European Journal of Heart Failure 2009 11(9):825-831; doi:10.1093/eurjhf/hfp105
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Plasma concentrations of tumour necrosis factor-alpha, tumour necrosis factor-related apoptosis-inducing ligand, and FasLigand/CD95L in patients with Chagas cardiomyopathy correlate with left ventricular dysfunction

Jamille Fernandes Lula1, Manoel Otavio da Costa Rocha2, Maria do Carmo Pereira Nunes2, Antônio Luiz Pinho Ribeiro2, Mauro Martins Teixeira3, Maria Terezinha Bahia1 and André Talvani1,*

1 Laboratório de doença de Chagas, Departamento de Ciências Biológicas & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus universitário, Morro do Cruzeiro, Ouro Preto, MG 35400-000, Brazil
2 Programa de Pós-Graduação em Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31130-1000, Brazil
3 Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil

* Corresponding author. Tel: +55 31 3559 1690, Fax: +55 31 3559 1680, Email: talvani{at}nupeb.ufop.br


  Abstract

Aims: Cardiomyocyte apoptosis is reported to be involved in the pathogenesis of human chronic Chagas cardiomyopathy (CCC). Members of the tumour necrosis factor (TNF) superfamily (TNF-{alpha}, FasLigand/CD95L, and TNF-related apoptosis-inducing ligand) are known to activate the death receptor pathway. We therefore investigated whether levels of TNF-{alpha}, FasLigand/CD95L, and TRAIL correlated with changes in heart function of patients with Chagas disease (n = 31).

Methods and results: Concentrations of TNF-{alpha} and TRAIL were clearly augmented in individuals with severe form CCC (n = 16). Levels of FasLigand/CD95L were greater in chagasic patients than in non-infected individuals (n = 15) but did not differentiate between clinical forms of Chagas disease. There was a good correlation between TNF-{alpha} (r = 0.85 and r = 0.68, P < 0.0001) or TRAIL (r = 0.68 and r = 0.60, P < 0.001) and left ventricular ejection fraction (LVEF) and left ventricular diastolic diameter (LVDD), respectively. In addition, TNF-{alpha} (r = 0.57, P = 0.0001), TRAIL (r = 0.56, P = 0.001), and FasLigand/CD95L (r = 0.51, P = 0.001) showed a good correlation with brain natriuretic peptide, a well-known parameter of ventricular dysfunction in CCC. There was a weak correlation between levels of FasLigand/CD95L (r = 0.50, P < 0.004) and both LVEF and LVDD. There was no correlation between levels of TNF superfamily ligands and chronotropic incompetence, maximal heart rate, or number of ventricular premature beats in 24 h.

Conclusion: Plasma levels of TNF superfamily ligands are elevated in patients with functional but not arrhythmogenic disturbances, and these death receptor ligands may be potential markers of ventricular dysfunction in CCC.

Key Words: Chagas cardiomyopathy • TNF-{alpha} • TRAIL • FasLigand/CD95L • BNP • Left ventricular dysfunction

Received March 26, 2009; Revised June 15, 2009; Accepted June 24, 2009


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