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.
Highlights
Chagas’ disease is a significant cause of morbidity and mortality in Central and South America, affecting about 13 million people [1]
We describe the protein profile of the myocardium from patients with chronic Chagas’ disease cardiomyopathy
Data from several differential proteome analyses in myocardial samples are available in the literature, the present study is the first report on the myocardial protein profile of chronic Chagas’ disease cardiomyopathy (CCC) patients
Summary
Chagas’ disease is a significant cause of morbidity and mortality in Central and South America, affecting about 13 million people [1]. Myocardial left ventricular free wall heart samples were obtained from two end-stage heart failure CCC patients with a diagnosis established by seropositivity to T. cruzi in at least two of three tests, i.e., ELISA, indirect immunofluorescence and indirect hemagglutination, and by positive epidemiology. Both patients were female and were 42 and 62 years old, with an ejection fraction
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