Changes in cellular contractility and cytokines profile during Trypanosoma cruzi infection in mice

Abstract

Trypanosoma cruzi, an intracellular protozoan parasite infecting a wide variety of vertebrates, is the agent responsible for Chagas' disease. This pathology often results in severe inflammatory heart condition and it is one of the major causes of dilated cardiomyopathy leading to heart failure in Latin America. Nevertheless, little is known about the changes in isolate cardiac myocytes contractility during the development of this pathology. Here we report a relationship between cytokines profile of mice infected with T. cruzi and the modifications in the cellular contractility pattern. We found that cellular contractility, measured as fractional shortening, showed a complex behavior. The changes were evaluated during the acute phase (15, 30 and 45 dpi) and chronic phase (>90 dpi). The time to half contraction and relaxation were lengthier despite the number of days after infection or the heart region evaluated. The maximal contraction and relaxation velocities were significantly slower. The observed changes in cellular contractility were correlated with the presence of circulating IFN-gamma, TNF-alpha and MCP-1/CCL2 during the course of infection. Together, our data demonstrate that cellular contractility is altered in the three heart regions studied, and these alterations are observed at the very beginning of the parasitism and they remained until the chronic phase has been reached. Indeed, we propose a role for IFN-gamma, TNF-alpha and MCP-1/CCL2 in the mechanical heart remodeling during experimental Chagas' disease.

Altered Cardiomyocyte Function and Trypanosoma cruzi Persistence in Chagas Disease

“…1 The onset of Chagas disease is divided in two stages: an acute phase, with high levels of T. cruzi in the bloodstream, and a chronic phase, in which the symptoms are observed 10-40 years after the infection, and approximately 20-30% of patients manifest heart conditions including, but not restricted to, heart hypertrophy, heart failure, and cardiac arrhythmias. 2,3 Changes in heart function is connected to a set of cellular and molecular changes in cardiac tissue such as disrupted myofibrils, increased myocyte apoptosis, 4 collagen deposition, 5 oxidative stress, 6 altered cellular metabolism, 7 reduced cellular contractility, 8 and disturbance of electrical properties of the heart. 9,10 There are distinct hypotheses to explain the molecular mechanisms of altered electrical and contractility properties of the heart during Chagas disease.…”

Cardiomyocyte dysfunction during the chronic phase of Chagas disease

“…Currently, 10 million people are infected and 25 million people live in areas where the infectious parasites are present (WHO 2010). However, until now, few studies have provided compelling evidence of cardiomyocyte dysfunction during the establishment of heart failure following infection by T. cruzi (de Carvalho et al 1992, Pacioretty et al 1995, Roman-Campos et al 2009b. Recently, new data have provided supporting evidence of how the left ventricular electrical-mechanical dysfunction observed during the initial stages of chagasic cardiomyopathy occurs (Esper et al 2012, RomanCampos et al 2012.…”

“…Adult left ventricular myocytes were enzymatically isolated using collagenase (1 mg/mL) with a calcium gradient method as previously described (Roman-Campos et al 2009b). Myocytes were freshly isolated and stored in Dulbecco's Modified Eagle's Medium until they were used for experiments (within 4-6 h).…”

“…To study the cellular mechanism of cardiomyocyte dysfunction during the chronic phase of Chagas disease, in which T. cruzi is no longer observed in the bloodstream (Roman-Campos et al 2009b), we first measured the transmembrane APs of cardiomyocytes isolated from Chagasic cardiomyopathy caused an increase in the time to AP repolarisation (APR). The lengths of time to 90% APR were 27.9 ± 2.2 ms (n = 13) and 36.2 ± 2.7 ms (n = 13) in control and infected mice, respectively (Fig.…”

Treinamento em natação atenua a disfução contrátil de cardiomiócitos de ratos diabéticos

“…Contraction measurements employed only those cardiomyocytes that were in good condition, with the edges and well-defined sarcomeric striations, at rest, with no voluntary contractions. The contractions were analyzed as described previously 19 .…”