Abstract
Chronic inflammation, as a consequence of the persistent infection with Trypanosoma cruzi, leads to continuous activation of the immune system in patients with chronic Chagas disease. We have previously shown that increased sera levels of soluble P-selectin are associated with the severity of the cardiomyopathy distinctive of chronic Chagas disease. In this study, we explored the expression of biomarkers of platelet and endothelial activation, tissue remodeling, and mediators of the coagulation cascade in patients at different clinical stages of chronic Chagas heart disease. The frequencies of activated platelets, measured by the expression of CD41a and CD62P were decreased in patients with chronic Chagas disease compared with those in uninfected subjects, with an inverse association with disease severity. Platelet activation in response to adenosine diphosphate was also decreased in T. cruzi-infected subjects. A major proportion of T. cruzi infected subjects showed increased serum levels of fibrinogen. Patients with severe cardiac dysfunction showed increased levels of endothelin-1 and normal values of procollagen I. In conclusion, chronic infection with T. cruzi induced hemostatic alterations, even in those patients who do not yet present cardiac symptoms.
Highlights
Trypanosoma cruzi, the causative agent of Chagas disease, infects 6–7 million people in Central and South America, as well as in countries historically nonendemic for T. cruzi infection [1]
Platelet levels measured by platelet counts were not altered in patients with chronic Chagas disease compared with uninfected subjects (Fig 1A)
After being activated by agonist including thrombin, collagen and adenosine diphosphate), the molecules stored in the alpha-granules in platelets or in the Weibel-Palade bodies in endothelial cells are exposed in the cell surface [16,27]
Summary
Trypanosoma cruzi, the causative agent of Chagas disease, infects 6–7 million people in Central and South America, as well as in countries historically nonendemic for T. cruzi infection [1]. The acute phase is characterized by the presence of a large number of parasites in the circulation and even though the immune response is able to control the infection, the parasite can survive establishing a chronic infection. As a consequence of the persistent infection with T. cruzi, leads to continuous activation of the immune system in chronic Chagas disease patients [2,3,4,5]. Biomarkers of altered microcirculation in chronic Chagas disease members of The National Scientific and Technical Research Council, Argentina. GC is a Ph.D. fellow of the Scientific and Technological Research Fund (FONCyT), Argentina
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