Cardiac MicroRNA Expression Profile After Experimental Brain Death Is Associated With Myocardial Dysfunction and Can Be Modulated by Hypertonic Saline.

Autor: Ferreira LRP; RNA Systems Biology Laboratory (RSBL), Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.; National Institute of Science and Technology for Vaccines (INCTV), Belo Horizonte, Minas Gerais, Brazil., Correia CJ; Laboratório Cirúrgico de Pesquisa Cardiovascular (LIM-11), Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Zanoni FL; Laboratório Cirúrgico de Pesquisa Cardiovascular (LIM-11), Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Carvalho-Silva AC; RNA Systems Biology Laboratory (RSBL), Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.; National Institute of Science and Technology for Vaccines (INCTV), Belo Horizonte, Minas Gerais, Brazil., Zaniratto R; Laboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Institute for Investigation in Immunology (INCT-iii), São Paulo, Brazil., da Silva Cândido D; Laboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Institute for Investigation in Immunology (INCT-iii), São Paulo, Brazil., Almeida RR; Laboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Institute for Investigation in Immunology (INCT-iii), São Paulo, Brazil., Breithaupt-Faloppa AC; Laboratório Cirúrgico de Pesquisa Cardiovascular (LIM-11), Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Cunha-Neto E; Laboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Institute for Investigation in Immunology (INCT-iii), São Paulo, Brazil.; Laboratório de Imunologia Clínica e Alergia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Moreira LFP; Laboratório Cirúrgico de Pesquisa Cardiovascular (LIM-11), Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Transplantation [Transplantation] 2022 Feb 01; Vol. 106 (2), pp. 289-298.
DOI: 10.1097/TP.0000000000003779
Abstrakt: Background: Brain death (BD) is associated with systemic inflammatory compromise, which might affect the quality of the transplanted organs. This study investigated the expression profile of cardiac microRNAs (miRNAs) after BD, and their relationship with the observed decline in myocardial function and with the changes induced by hypertonic saline solution (HSS) treatment.
Methods: Wistar rats were assigned to sham-operation (SHAM) or submitted to BD with and without the administration of HSS. Cardiac function was assessed for 6 h with left ventricular (LV) pressure-volume analysis. We screened 641 rodent miRNAs to identify differentially expressed miRNAs in the heart, and computational and functional analyses were performed to compare the differentially expressed miRNAs and find their putative targets and their related enriched canonical pathways.
Results: An enhanced expression in canonical pathways related to inflammation and myocardial apoptosis was observed in BD induced group, with 2 miRNAs, miR-30a-3p, and miR-467f, correlating with the level of LV dysfunction observed after BD. Conversely, HSS treated after BD and SHAM groups showed similar enriched pathways related to the maintenance of heart homeostasis regulation, in agreement with the observation that both groups did not have significant changes in LV function.
Conclusions: These findings highlight the potential of miRNAs as biomarkers for assessing damage in BD donor hearts and to monitor the changes induced by therapeutic measures like HSS, opening a perspective to improve graft quality and to better understand the pathophysiology of BD. The possible relation of BD-induced miRNA's on early and late cardiac allograft function must be investigated.
Competing Interests: The authors declare no conflicts of interest.
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Databáze: MEDLINE