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

• Published in: International journal of molecular sciences Vol. 20; no. 16; p. 4064
• Main Authors: Nonaka, Carolina Kymie Vasques, Macêdo, Carolina Thé, Cavalcante, Bruno Raphael Ribeiro, Alcântara, Adriano Costa de, Silva, Daniela Nascimento, Bezerra, Milena da Rocha, Caria, Alex Cleber Improta, Tavora, Fábio Rocha Fernandes, Neto, João David de Souza, Noya-Rabelo, Márcia Maria, Rogatto, Silvia Regina, Ribeiro Dos Santos, Ricardo, Souza, Bruno Solano de Freitas, Soares, Milena Botelho Pereira
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-08-2019; MDPI
• Subjects: Biomarkers; Biomarkers - chemistry; Biomarkers - metabolism; Cardiomyocytes; Cardiomyopathy; Cell size; Chagas Cardiomyopathy - genetics; Chagas Cardiomyopathy - metabolism; Chagas Cardiomyopathy - pathology; Chagas disease; Correlation analysis; Damage detection; Disease; Eutrophication; Female; Fibroblasts; Fibrosis; Fibrosis - genetics; Fibrosis - metabolism; Fibrosis - pathology; Gene expression; Heart diseases; Heart failure; Humans; Hypertrophy; inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Male; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Phenotypes; Protozoa; ROC Curve; Trypanosoma cruzi; Ventricle; Ventricular Remodeling - genetics; Ventricular Remodeling - physiology; microRNA; fibrosis; chagas disease; cardiomyopathy; inflammation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20164064

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 (
= 28), CD indeterminate form (
= 10) and healthy controls (
= 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.