ardiac MicroRNA Expression Profile After Experimental Brain Death Is Associated With Myocardial Dysfunction and Can Be Modulated by Hypertonic Salin

Author(s)

Pinto Ferreira, Ludmila Rodrigues ^{[1, 2]} ; Correia, Cristiano Jesus ^[3] ; Zanoni, Fernando Luiz ^[3] ; Carvalho-Silva, Ana Carolina ^{[1, 2]} ; Zaniratto, Ricardo ^{[4, 5]} ; Candido, Darlan da Silva ^{[4, 5]} ; Almeida, Rafael Ribeiro ^{[4, 5]} ; Breithaupt-Faloppa, Ana Cristina ^[3] ; Cunha-Neto, Edecio ^{[4, 5, 6]} ; Moreira, Luiz Felipe P. ^[3]

Affiliation

^[1] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Morfol, RNA Syst Biol Lab RSBL, Belo Horizonte, MG - Brazil

^[2] Natl Inst Sci & Technol Vaccines INCTV, Belo Horizonte, MG - Brazil

^[3] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Inst Coracao InCor, Lab Cirurg Pesquisa Cardiovasc, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Inst Coracao InCor, Lab Imunol, Sao Paulo - Brazil

^[5] Inst Invest Immunol INCT Iii, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Fac Med, Lab Imunol Clin & Alergia, Sao Paulo - Brazil

• Document type: Journal article
• Source: TRANSPLANTATION; v. 106, n. 2, p. 289-298, FEB 2022.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 13/50302-3 - Identification of predictive / prognostic genetic signature in Chagas cardiomyopathy: a systems biology approach
• Grantee: Edecio Cunha Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/19841-2 - Study of the effects of hypertonic saline solution on microcirculatory and cardiac tissue changes, and development of the inflammatory process in a rat model of brain death
• Grantee: Luiz Felipe Pinho Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50890-5 - INCT of Investigation in Immunology
• Grantee: Jorge Elias Kalil Filho
• Support Opportunities: Research Projects - Thematic Grants