Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

Autor(es)

P.C. Teixeira ; L.K. Iwai ; A.C.K. Kuramoto ; R. Honorato ^[4] ; A. Fiorelli ^[5] ; N. Stolf ^[6] ; J. Kalil ; E. Cunha-Neto

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 39, n. 12, p. 1549-1562, 2006-10-30.

Resumo

Chronic Chagas' disease cardiomyopathy (CCC) is an often fatal outcome of Trypanosoma cruzi infection, with a poorer prognosis than other cardiomyopathies. CCC is refractory to heart failure treatments, and is the major indication of heart transplantation in Latin America. A diffuse myocarditis, plus intense myocardial hypertrophy, damage and fibrosis, in the presence of very few T. cruzi forms, are the histopathological hallmarks of CCC. To gain a better understanding of the pathophysiology of CCC, we analyzed the protein profile in the affected CCC myocardium. Homogenates from left ventricular myocardial samples of end-stage CCC hearts explanted during heart transplantation were subjected to two-dimensional electrophoresis with Coomassie blue staining; protein identification was performed by MALDI-ToF mass spectrometry and peptide mass fingerprinting. The identification of selected proteins was confirmed by immunoblotting. We demonstrated that 246 proteins matched in gels from two CCC patients. They corresponded to 112 distinct proteins. Along with structural/contractile and metabolism proteins, we also identified proteins involved in apoptosis (caspase 8, caspase 2), immune system (T cell receptor ß chain, granzyme A, HLA class I) and stress processes (heat shock proteins, superoxide dismutases, and other oxidative stress proteins). Proteins involved in cell signaling and transcriptional factors were also identified. The identification of caspases and oxidative stress proteins suggests the occurrence of active apoptosis and significant oxidative stress in CCC myocardium. These results generated an inventory of myocardial proteins in CCC that should contribute to the generation of hypothesis-driven experiments designed on the basis of the classes of proteins identified here. (AU)

• Processo FAPESP: 00/14549-4 - Desenvolvimento de vacina contra o estreptococo beta hemolítico do grupo A
• Beneficiário: Luiza Guglielmi
• Modalidade de apoio: Auxílio à Pesquisa - Parceria para Inovação Tecnológica - PITE
• Processo FAPESP: 01/00729-3 - Identificação de fatores virológicos, genéticos e imunológicos associados ao fenótipo de não progressão da doença do HIV: estudo de marcadores de virulência do HIV, genotipagem de co-receptor CCR5, e expressão de painel abrangente de citocinas (cDNA microarrays) em amostras de sangue periférico de pacientes portadores do HIV não progressores e progressores acompanhados na Casa da AIDS
• Beneficiário: Edecio Cunha Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/15322-4 - Alterações do metabolismo energético e indução do fenótipo hipertrófico no miocárdio de pacientes com cardiopatia chagásica crônica: papel do interferon-gama
• Beneficiário: Priscila Camillo Teixeira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto