Abstract
Chronic Chagas’ disease affects 10–30 % of patients infected with Trypanosoma cruzi, and it mainly manifests as cardiomyopathy. Important pathophysiological mechanisms involved in the cardiac lesions include activation of the endothelium and induced microvascular alterations. These processes involve the production of endothelial adhesion molecules and thromboxane A2, which are involved in inflammatory cell recruitment and platelet aggregation, respectively. Cyclooxygenase inhibitors such as aspirin decrease thromboxane production and alter the course of Chagas’ disease, both in the acute and chronic phases. We studied the effects of the administration of low and high doses of aspirin during the early phase of T. cruzi infection, following microvascular damage in the context of a chronic murine model of Chagas’ disease. The effects of both schedules were assessed at 24 and 90 days postinfection by evaluating parasitemia, mortality, and cardiac histopathological changes as well as the expression of ICAM, VCAM, and E-selectin in cardiac tissue. Thromboxane A2, soluble ICAM, and E-selectin blood levels were also measured. While aspirin did not affect parasitemia or mortality in the infected mice, it decreased both cardiac inflammatory infiltrates and thromboxane levels. Additionally, at 90 days postinfection, aspirin normalized sICAM and sE-selectin levels. Considering the improved endothelial function induced by aspirin, we propose the possibility of including this drug in clinical therapy to treat chronic Chagas’ disease.
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Acknowledgments
This work was supported by grants from Fondo Nacional de Ciencia y Tecnología Chile (Grant numbers 1090078, 1120230, and 1090124) and a grant from Consejo Nacional de Ciencia y Tecnologia—Programa de Investigacion Asociativa Chile (Grant Anillo ACT112). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Molina-Berríos, A., Campos-Estrada, C., Lapier, M. et al. Protection of vascular endothelium by aspirin in a murine model of chronic Chagas’ disease. Parasitol Res 112, 2731–2739 (2013). https://doi.org/10.1007/s00436-013-3444-x
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DOI: https://doi.org/10.1007/s00436-013-3444-x