Matrix metalloproteinases 2 and 9 are differentially expressed in patients with indeterminate and cardiac clinical forms of Chagas disease.

Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8(+) T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules.

Retrospective cohort study to evaluate the continuous use of anticholesterolemics and diuretics in patients with COVID-19.

Purpose: The purpose of this study is to evaluate the interference of the continuous use of drug classes in the expression of biomarkers during the first week of hospitalization and in the prognosis of patients with COVID-19. Methods: The patients diagnosed with COVID-19 and confirmed with SARS-CoV-2 by RT-qPCR assay underwent the collection of fasting whole blood samples for further analysis. Other data also extracted for this study included age, sex, clinical symptoms, related comorbidities, smoking status, and classes of continuous use. Routine serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, N-terminal fragment of B-type natriuretic peptide, and cardiac troponin, were measured. Results: In this cross-sectional study, a total of 176 patients with COVID-19 hospitalizations were included. Among them, 155 patients were discharged (88.5%), and 21 patients died (12%). Among the drug classes evaluated, we verified that the continuous use of diuretic 4.800 (1.853-11.67) (p = 0.0007) and antihypercholesterolemic 3.188 (1.215-7.997) (p = 0.0171) drug classes presented a significant relative risk of death as an outcome when compared to the group of patients who were discharged. We evaluated biomarkers in patients who used continuous antihypercholesterolemic and diuretic drug classes in the first week of hospitalization. We observed significant positive correlations between the levels of CRP with cardiac troponin (r = 0.714), IL-6 (r = 0.600), and IL-10 (r = 0.900) in patients who used continuous anticholesterolemic and diuretic drug classes and were deceased. In these patients, we also evaluated the possible correlations between the biomarkers AST, NT-ProBNP, cardiac troponin, IL-6, IL-8, and IL-10. We observed a significantly negative correlations in AST levels with NT-ProBNP (r = -0.500), cardiac troponin (r = -1.00), IL-6 (r = -1.00), and IL-10 (r = -1.00) and a positive correlation with IL-8 (r = 0.500). We also observed significant negative correlation in the levels of NT-ProBNP with IL-10 (r = -0.800) and a positive correlation with cardiac troponin (r = 0.800). IL-6 levels exhibited positive correlations with cardiac troponin (r = 0.800) and IL-10 (r = 0.700). Conclusion: In this study, we observed that hospitalized COVID-19 patients who continued using anticholesterolemic and diuretic medications showed a higher number of correlations between biomarkers, indicating a poorer clinical prognosis. These correlations suggest an imbalanced immune response to injuries caused by SARS-CoV-2.

Plasma cytokine expression is associated with cardiac morbidity in chagas disease.

The expression of immune response appears to be associated with morbidity in Chagas disease. However, the studies in this field have usually employed small samples of patients and statistical analyses that do not consider the wide dispersion of cytokine production observed in these patients. The aim of this study was to evaluate the plasma cytokine levels in well-defined clinical polar groups of chagasic patients divided into categories that better reflect the wide cytokine profile and its relationship with morbidity. Patients infected with Trypanosoma cruzi (T. cruzi) were grouped as indeterminate (IND) and cardiac (CARD) forms ranging from 23 to 69 years of age (mean of 45.6±11.25). The IND group included 82 individuals, ranging from 24 to 66 years of age (mean of 39.6±10.3). The CARD group included 94 patients ranging from 23 to 69 years of age (mean of 48±12.52) presenting dilated cardiomyopathy. None of the patients have undergone chemotherapeutic treatment, nor had been previously treated for T. cruzi infection. Healthy non-chagasic individuals, ranging from 29 to 55 years of age (mean of 42.6±8.8) were included as a control group (NI). IND patients have a higher intensity of interleukin 10 (IL-10) expression when compared with individuals in the other groups. By contrast, inflammatory cytokine expression, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 beta (IL-1ß), proved to be the highest in the CARD group. Correlation analysis showed that higher IL-10 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Altogether, these findings reinforce the concept that a fine balance between regulatory and inflammatory cytokines represents a key element in the establishment of distinct forms of chronic Chagas disease.