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

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.

Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy

“…Proteomic profiling of myocardium from CCC patients revealed that 27 % of identified proteins belong to energy metabolism pathways [27]. Using gene expression profiling, our group found differential expression of a significant number of genes involved in oxidative phosphorylation and lipid catabolism in myocardial samples from CCC patients, but not in samples from patients with dilated cardiomyopathy, when compared to samples from subjects without cardiomyopathy [15].…”

Chagas Disease Cardiomyopathy: Immunopathology and Genetics

“…Gene expression profiling also disclosed that lipid metabolism and mitochondrial oxidative phosphorylation genes were selectively modulated in CCC myocardial tissue, suggesting a specific energy imbalance. Using proteomic analysis (bidimensional electrophoresis and MALDI-TOF mass spectrometry), our group has established a proteomic inventory of >100 distinct myocardial proteins in CCC myocardial tissue [46]. Preliminary data from differential protein expression analysis in the myocardium of CCC, DCM, and ischemic cardiomyopathy (IC) patients as compared to control heart donor myocardial samples allowed the identification of prominently altered pathways, including cardiac remodeling and depressed energy metabolism.…”

Chagas disease cardiomyopathy: current concepts of an old disease

“…Our group has recently described an inventory of myocardial proteins from patients with severe CCC. This has allowed us to identify proteins with high and low abundance in the tissue, including proteins with structural, metabolic, stress, apoptosis and immune response functions (TEIXEIRA et al, 2006). It would be interesting to investigate whether the expression of cardiac proteins differs between severe CCC patients and mild CCC or IND subjects.…”