Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy.

Carolina Kymie Vasques Nonaka,Carolina Kymie Vasques Nonaka,Carolina Thé Macêdo,Bruno Solano De Freitas Souza,Bruno Raphael Ribeiro Cavalcante,Bruno Raphael Ribeiro Cavalcante,Fábio Rocha Fernandes Tavora,Milena Botelho Pereira Soares,Milena Botelho Pereira Soares,Ricardo Ribeiro Dos Santos,Ricardo Ribeiro Dos Santos,Daniela Nascimento Silva,Daniela Nascimento Silva,Alex Cleber Improta Caria,Alex Cleber Improta Caria,Milena Da Rocha Bezerra,Silvia Regina Rogatto,Márcia Maria Noya-Rabelo,João David De Souza Neto,Adriano Costa De Alcântara

doi:10.3390/ijms20164064

Abstract

Chagas disease (CD) affects approximately 6–7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.

Highlights

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects approximately 6–7 million people worldwide mainly in Latin American countries, and is spreading to other continents due to population migration [1]
The majority of infected patients will remain asymptomatic during the chronic phase, in what is known as the indeterminate form of Chagas disease, while approximately 30% will develop the cardiac form, known as chronic Chagas disease Cardiomyopathy (CCC), with a high rate of morbidity and mortality [2]
We evaluated the expression profile of circulating microRNAs in three groups: subjects with CCC, subjects with indeterminate form of Chagas disease, and healthy controls, in order to identify possible correlations with clinical parameters associated with the disease prognosis

Summary

Introduction

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects approximately 6–7 million people worldwide mainly in Latin American countries, and is spreading to other continents due to population migration [1]. The majority of infected patients will remain asymptomatic during the chronic phase, in what is known as the indeterminate form of Chagas disease, while approximately 30% will develop the cardiac form, known as chronic Chagas disease Cardiomyopathy (CCC), with a high rate of morbidity and mortality [2]. In the cardiac form, myocardial dysfunction occurs due to parasite persistence, chronic inflammation [4,5], and cardiac fibrosis [6]. Currently available diagnostic tests are capable of adequately identifying infected patients, there is no biomarker that can predict the individual risk for a patient’s potential to progress from the indeterminate form to CCC [8]. The identification of novel biomarkers allowing for early identification of myocardial damage is desirable for interventions aiming at delaying heart dysfunction development and progression

Methods

Results

Conclusion