Abstract
Chagas disease is caused by Trypanosoma cruzi which is endemic in Latin America. T. cruzi infection results in a latent infection with approximately a third of latently infected patients developing chronic Chagas cardiomyopathy (CCM). CCM is a common cause of cardiomyopathy in endemic regions and has a poor prognosis compared to other cardiomyopathies. The factors responsible for the transition from the asymptomatic indeterminate latent stage of infection to CCM are poorly understood. Our previous studies demonstrated that lipid metabolism and diet are important determinants of disease progression. In the present study, we analyzed various serum metabolomic biomarkers such as acylcarnitines, amino acids, biogenic amines, glycerophospholipids, and sphingolipids in murine models of CCM, where the mice specifically develop either left or right ventricular cardiomyopathy based on the diets fed during the indeterminate stage in a murine model of Chagas disease. Our data provide new insights into the metabolic changes that may predispose patients to CCM and biomarkers that may help predict the risk of developing cardiomyopathy from T. cruzi infection. Author Summary. Chronic Chagas cardiomyopathy (CCM) is a parasitic disease prevalent in Latin America. Currently, no effective drugs or vaccines are available to prevent or cure CCM. The factors involved in the disease severity and progression are poorly understood to design new therapeutic interventions. In order to rapidly identify Chagas patients with a higher risk to develop CCM, a new set of biomarkers specific to Chagas disease is needed. We performed serum metabolomic analyses in chronic T. cruzi-infected mice fed on different diets and identified cardiac ventricular-specific metabolite biomarkers that could define CCM severity. In this paper, we present the results of serum metabolomic analyses and discuss its correlations to the diet-induced metabolic regulations in the pathogenesis of CCM in a murine model of Chagas disease.
Highlights
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic to Latin America, where approximately 8-10 million people are infected [1]
Following the acute phase of infection, most infected individuals enter into a prolonged asymptomatic form of disease termed the “chronic indeterminate phase,” which can persist for life without developing Chagas-related symptoms [2]; approximately 30% of “chronic indeterminate phase” individuals will develop debilitating and sometimes lifethreatening Chagas-related symptoms including chronic Chagas cardiomyopathy (CCM) [3]
To understand further the effect of diet on plasma metabolites and its link to cardiomyopathy with either left ventricle (LV) or right ventricle (RV) dysfunction in T. cruzi-infected mice, we analyzed plasma metabolomic profiles of infected mice on different diets
Summary
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic to Latin America, where approximately 8-10 million people are infected [1]. Chagas disease is a major cause of heart disease and cardiovascular-related deaths in Latin America. Chronic Chagas cardiomyopathy is characterized by its various degrees of severity, and Chagas patients have a Disease Markers poorer prognosis than non-Chagas cardiac patients [5]. The lack of prognosis and progression markers for chronic Chagas disease is a barrier for testing new drugs to prevent the progression of cardiomyopathy. Several inflammatory and protein molecules such as NT-proBNP and Hs-cTnT have been identified as diagnostic biomarkers in distinguishing the severity of CCM [6, 7], but these markers are not specific to this cardiomyopathy [8]. There has been a lack of biomarker identification for Chagas disease severity-specific biomarkers that could predict the risk of developing cardiac dysfunction/cardiomyopathy during the asymptomatic indeterminate phase. Identification and development of such biomarkers would help to develop strategies to prevent the transition from indeterminate to symptomatic stage
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
