MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy

作者：Pinto Ferreira Ludmila Rodrigues; Frade Amanda Farage; Barros Santos Ronaldo Honorato; Teixeira Priscila Camillo; Baron Monique Andrade; Navarro Isabela Cunha; Benvenuti Luiz Alberto; Fiorelli Alfredo Inacio; Bocchi Edimar Alcides; Stolf Noedir Antonio; Chevillard Christophe; Kalil Jorge; Cunha Neto Edecio^*

来源：International Journal of Cardiology, 2014, 175(3): 409-417.

DOI：10.1016/j.ijcard.2014.05.019

• Chagas disease
• Trypanosoma cruzi
• miRNA
• Heart

Background/methods: Chagas disease is caused by an intracellular parasite, Trypanosoma cruzi, and it is a leading cause of heart failure in Latin America. The main clinical consequence of the infection is the development of a Chronic Chagas disease Cardiomyopathy (CCC), which is characterized by myocarditis, hypertrophy and fibrosis and affects about 30% of infected patients. CCC has a worse prognosis than other cardiomyopathies, like idiopathic dilated cardiomyopathy (DCM). It is well established that myocardial gene expression patterns are altered in CCC, but the molecular mechanisms underlying these differences are not clear. MicroRNAs are recently discovered regulators of gene expression, and are recognized as important factors in heart development and cardiovascular disorders (CD). We analyzed the expression of nine different miRNAs inmyocardial tissue samples of CCC patients in comparison to DCM patients and samples from heart transplant donors. Using the results of a cDNA microarray database on CCC and DCM myocardium, signaling networks were built and nodal molecules were identified. Results: We observed that five miRNAs were significantly altered in CCC and three in DCM; importantly, three miRNAs were significantly reduced in CCC as compared to DCM. We observed that multiple gene targets of the differentially expressed miRNAs showed a concordant inverse expression in CCC. Significantly, most gene targets and involved networks belong to crucial disease-related signaling pathways. Conclusion: These results suggest that miRNAs may play a major role in the regulation of gene expression in CCC pathogenesis, with potential implication as diagnostic and prognostic tools.

• 出版日期2014-8-20