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

1
Center for Biotechnology and Cell Therapy, Hospital São Rafael, 41253-190 Salvador, Brazil
2
Gonçalo Moniz Institute, FIOCRUZ, 40296-710 Salvador, Brazil
3
D’Or Institute for Research and Education (IDOR), 22281-100 Rio de Janeiro, Brazil
4
Department of Cardiology, São Rafael Hospital, 41253-190 Salvador, Brazil
5
Federal University of Bahia, UFBA, 40231-300 Salvador, Brazil
6
Messejana Hospital, 60846-190 Fortaleza, Brazil
7
Department of Clinical Genetics, Vejle Hospital, Institute of Regional Health Research, University of Southern Denmark, 7100 Vejle, Denmark
8
National Institute of Science and Technology for Regenerative Medicine, 21941-902 Rio de Janeiro, Brazil
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4064; https://doi.org/10.3390/ijms20164064
Received: 10 May 2019 / Revised: 11 July 2019 / Accepted: 14 July 2019 / Published: 20 August 2019
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. View Full-Text
Keywords: chagas disease; cardiomyopathy; microRNA; fibrosis; inflammation chagas disease; cardiomyopathy; microRNA; fibrosis; inflammation
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Nonaka, C.K.V.; Macêdo, C.T.; Cavalcante, B.R.R.; Alcântara, A.C.; Silva, D.N.; Bezerra, M.R.; Caria, A.C.I.; Tavora, F.R.F.; Neto, J.D.S.; Noya-Rabelo, M.M.; Rogatto, S.R.; Ribeiro dos Santos, R.; Souza, B.S.F.; Soares, M.B.P. Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy. Int. J. Mol. Sci. 2019, 20, 4064.

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