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

Author(s)

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

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 39, n. 12, p. 1549-1562, 2006-10-30.

Abstract

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)

• FAPESP's process: 00/14549-4 - Development of a vaccine against group A beta hemolytic Streptococcus
• Grantee: Luiza Guglielmi
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• FAPESP's process: 01/00729-3 - Identification of virological, genetic and immunological factors associated with the phenotype of HIV disease non-progression: a study of HIV virulence markers, CCR5 co-receptor genotyping and expression of broad panel of cytokines (cDNA microarrays) in peripheral blood samples of patients with HIV progressors and non-progressors followed up at Casa da AIDS [SIDA Healthcare Services]
• Grantee: Edecio Cunha Neto
• Support Opportunities: Regular Research Grants