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2018 ; 22
(1
): 68
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Exosomes from patients with septic shock convey miRNAs related to inflammation
and cell cycle regulation: new signaling pathways in sepsis?
#MMPMID29540208
Real JM
; Ferreira LRP
; Esteves GH
; Koyama FC
; Dias MVS
; Bezerra-Neto JE
; Cunha-Neto E
; Machado FR
; Salomão R
; Azevedo LCP
Crit Care
2018[Mar]; 22
(1
): 68
PMID29540208
show ga
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.