Research Article: Impaired frequencies and function of platelets and tissue remodeling in chronic Chagas disease

Date Published: June 14, 2019

Publisher: Public Library of Science

Author(s): Claudia Pengue, Gonzalo Cesar, María Gabriela Alvarez, Graciela Bertocchi, Bruno Lococo, Rodolfo Viotti, María Ailén Natale, Melisa D. Castro Eiro, Silvia S. Cambiazzo, Nancy Perroni, Myriam Nuñez, María Cecilia Albareda, Susana A. Laucella, Pablo Garcia de Frutos.

http://doi.org/10.1371/journal.pone.0218260

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.

Partial Text

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.

Platelets, which participate in thrombotic processes, have different roles in vascular biology and in the immune response, including protective functions and other functions that would contribute to an adverse inflammatory state [26]. Our results showed alterations in the levels and function of platelets, tissue remodeling and endothelial activation in chronically infected patients, even in those patients who do not yet present with cardiac symptoms. The negative trend between the percentages of platelets and disease severity might be explained either by a platelet activation with shortening of survival or by impaired platelet production in the bone marrow. P-selectin (CD62P) is a protein that mediates adhesion of leukocytes to the endothelium and in the aggregation of platelets. 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].

 

Source:

http://doi.org/10.1371/journal.pone.0218260

 

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