Abstract
One of the major challenges in chronic Chagas disease is to understand the mechanisms that predict the clinical evolution from asymptomatic to severe cardiac clinical forms. Our cohort consisted of twenty-eight Chagas disease patients followed for twenty years. Plasma levels of MMP-2 and MMP-9 gelatinases and TIMPs were evaluated by multiplexed immunoassay at two points in time with an average interval of six years. MMP-2 plasma levels, but not MMP-9, increased in cardiac patients over time. TIMP-1 levels diminished in cardiac patients, while TIMP-3 dropped in asymptomatic patients in the course of the evaluated interval. An inversion of time lines was observed relative to the clinical asymptomatic and cardiac forms for MMP-2. Receiver Operating Characteristic (ROC) curve analysis identified MMP-2 as a biomarker to distinguish asymptomatic from cardiac clinical forms, while MMP-9 is a biomarker that segregates infected from non-infected patients. We have pointed out that MMP-2 and MMP-9 together can predict clinical evolution in Chagas disease. MMP-2 was suggested as a biomarker for fibrosis replacement in early remodeling and a sensitive predictor for initial changes in asymptomatic patients that may evolve into the cardiac clinical form. MMP-9 seems to be a biomarker for late fibrosis and severe cardiac remodeling in cardiac patients.
Highlights
IntroductionAmerican trypanosomiasis, is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi[1]
Chagas disease, or American trypanosomiasis, is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi[1]
When we evaluated the proportion between times, we observed that NI and indeterminate form (IND) showed a higher proportion of matrix metalloproteinases (MMPs)-2 in T1, while the cardiac form (CARD) and EV groups showed a higher proportion in T0 (Fig. 1A)
Summary
American trypanosomiasis, is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi[1]. Human Chagas disease shows a variable clinical presentation. Whereas most T. cruzi infected patients persist in IND indefinitely, about 40% of them may develop lesions in different organs 10–30 years after initial infection, principally in the heart, the cardiac form (CARD) of the disease[6,7]. One of the major challenges in chronic Chagas disease is to identify a mechanism of intervention that is capable of predicting the clinical evolution of IND to CARD or minimizing the effects of fibrosis developing in the heart. Our group has previously described that matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are potential biomarkers of chronic changes in Chagas heart disease[8,9,10]. MMPs participate in the inflammatory process due to their proteolytic activity in cytokine activation[15]
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