Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Real, Juliana Monte [1, 2, 3] ; Pinto Ferreira, Ludmila Rodrigues [4, 5] ; Esteves, Gustavo Henrique [6] ; Koyama, Fernanda Christtanini [7, 1] ; Salles Dias, Marcos Vincius [8] ; Bezerra-Neto, Joao Evangelista [2] ; Cunha-Neto, Edecio [9, 5] ; Machado, Flavia Ribeiro [10] ; Salomao, Reinaldo [10] ; Pontes Azevedo, Luciano Cesar [1, 11]
Total Authors: 10
Show less -
[1] Hosp Sirio Libanes, Res & Educ Inst, Rua Prof Daher Cutait 69, BR-01539001 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Sao Paulo State Canc Inst, Sao Paulo - Brazil
[3] Hosp Serv Publ Estadual Sao Paulo, Sao Paulo - Brazil
[4] Univ Fed Minas Gerais, Inst Ciencias Biol, Morphol Dept, Belo Horizonte, MG - Brazil
[5] Univ Sao Paulo, Sch Med, Heart Inst, Lab Immunol, Sao Paulo - Brazil
[6] Univ Estadual Paraiba, Ctr Ciencias & Tecnol, Campina Grande - Brazil
[7] Ludwig Inst Canc Res, Sao Paulo - Brazil
[8] AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo - Brazil
[9] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo - Brazil
[10] Univ Fed Sao Paulo, Sao Paulo - Brazil
[11] Univ Sao Paulo, Emergency Med, Sao Paulo - Brazil
Total Affiliations: 11
Document type: Journal article
Source: CRITICAL CARE; v. 22, MAR 15 2018.
Web of Science Citations: 12

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; PRDX3, 2.6-fold; SOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-fold; SELS, 16-fold; GLRX2, 3.4-fold). The expression of myeloperoxidase mRNA remained elevated after 7 days (65-fold). Conclusions: Exosomes from patients with septic shock convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response, oxidative stress, and cell cycle regulation. Exosomes may represent a novel mechanism for intercellular communication during sepsis. (AU)

FAPESP's process: 10/52554-1 - Evaluation of micro RNA profile and expression of genes related to oxidative stress and inflammatory response in septic patients' microparticles
Grantee:Luciano Cesar Pontes de Azevedo
Support Opportunities: Regular Research Grants