MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva

• Ano de defesa: 2020
• Autor(a) principal: Souza-Siqueira, Talita
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Cruzeiro do Sul; Brasil; Programa de Pós Graduação Interdisciplinar em Ciências da Saúde; Cruzeiro do Sul
• Palavras-chave em Português: Inflamação; miR-15b-5p; miR-146a-5p; miR-223-3p; miR-195-5p; Septicemia.; CNPQ::CIENCIAS DA SAUDE
• Link de acesso: https://repositorio.cruzeirodosul.edu.br/handle/123456789/922

Despite the studies already carried out on plasma microRNAs (miRNAs) in sepsis, they are not well known about changes in their expression after hospital discharge. This study aimed to evaluate septic individuals extracellular plasma vesicles (EVs) proteins and miRNAs in six phases: a) acute phase (between the first and the 4th day of hospitalization), b) at the time of Intensive Care Unit (ICU) discharge and c) 3 months after ICU discharge, d) 6 months, e) 12 months, and f) 3 years. The miRNA's results were correlated with the cytokines (pro- and anti-inflammatory) plasma concentrations. The patients developed a low-level baseline chronic inflammation state as compared to the control group with slightly increased plasma levels of IL-6, IL-8 and C reactive protein even 3 months after ICU discharge. Plasma EVs isolated by ultracentrifugation had the size and protein composition expected. The protein composition was different between the states of health and sepsis and between the survivors and the ones who died. According to the proteomics, the plasma EVs originated from the lymphoid system, B lymphocytes and spleen, bone morrow, and hepatocytes. The following 15 miRNAs were found in the plasma EVs from septic patients and controls: miR-15b-5p, -16-5p, -20a-5p, -25-3p, -27a-3p, -29a-3p, -30d- 5p, -93-5p, -146a-5p, -148a -3p, -191-5p, -195-5p, and -223-3p. The reduction in the expression of thirteen miRNAs (miR-15b-5p, -16-5p, -20a-5p, -25-3p, -27a-3p, -29a- 3p, -30d-5p, -93-5p, -146a-5p, -148a-3p, -191-5p, -195-5p e -223-3p) during the acute phase (ICU internment) was more pronounced in the patients who died than in the survivors. These 13 miRNAs maybe used as plasma biomarkers of survival prognosis in sepsis. The reduction in expression of the miRNAs -15b-5p, -16-5p, -25- 3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -195-5p, and -223-3p during the acute phase remained for up to one year after ICU discharge but it was abolished after three years, reaching the control levels. These 9 miRNAs can then be used as plasma biomarkers of evolution and recovery of septic patients after hospital discharge.