Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?

• Autor(a) principal: Real, Juliana Monte
• Data de Publicação: 2018
• Outros Autores: Ferreira, Ludmila Rodrigues Pinto, Esteves, Gustavo Henrique, Koyama, Fernanda Christtanini, Dias, Marcos Vinicius Salles, Bezerra-Neto, Joao Evangelista, Cunha-Neto, Edecio, Machado, Flavia Ribeiro [UNIFESP], Salomão, Reinaldo [UNIFESP], Azevedo, Luciano Cesar Pontes
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/001300000n0kg
• Texto Completo: http://dx.doi.org/10.1186/s13054-018-2003-3; https://repositorio.unifesp.br/handle/11600/55813
• topic: Sepsis; Extracellular vesicles; Exosomes; MicroRNAs; Messenger RNA; Inflammatory response; Oxidative stress

Background: Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock. Methods: Blood samples were collected from 24 patients with septic shock at ICU admission and after 7 days of treatment. Twelve healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, and their miRNA and mRNA content was evaluated by qRT-PCR array. Results: As compared with healthy volunteers, exosomes from patients with sepsis had significant changes in 65 exosomal miRNAs. Twenty-eight miRNAs were differentially expressed, both at enrollment and after 7 days, with similar kinetics (18 miRNAs upregulated and 10 downregulated). At enrollment, 35 differentially expressed miRNAs clustered patients with sepsis according to survival. The pathways enriched by the miRNAs of patients with sepsis compared with control subjects were related mostly to inflammatory response. The comparison of miRNAs from patients with sepsis according to hospital survival demonstrated pathways related mostly to cell cycle regulation. At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-fold