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<p>The early sequence of respiratory failure events after the onset of sepsis is still unknown. We hypothesize that the lung should signal through circulating extracellular vesicles (EVs) when it is affected by a systemic inflammatory response. Blood samples were obtained from septic patients with (<i>n</i> = 5) and without acute respiratory distress syndrome (ARDS) (<i>n</i> = 13) at 24&#xa0;h of intensive care unit admission and 3 days later at Sírio-Libanês Hospital. Pulmonary-originated sepsis was not considered. The characteristics of the plasma-isolated EVs were compatible with exosomes. 48 miRNAs were evaluated by real-time PCR. Comparing all samples from patients with sepsis + ARDS to sepsis only, 9 miRNAs are transported in smaller amounts: miR-766 (-35.7, <i>p</i> = 0.002), miR-127 (-23.8, <i>p</i> = 0.001), miR-340 (-13.5, <i>p</i> = 0.006), miR-29b (-12.8, <i>p</i> = 0.001), miR-744 (-7.1, <i>p</i> = 0.05), miR-618 (-4.0, <i>p</i> = 0.02), miR-598 (-3.8, <i>p</i> = 0.035), miR-1260 (-2.5, <i>p</i> = 0.035); and miR-885-5p is expressed at higher levels (9.5; <i>p</i> = 0.028). In paired samples, the set of altered miRNAs is generally different (<i>p</i> &lt; 0.05) between sepsis + ARDS (miR-1183,-1267,-1290,-17,-192,-199a-3p,-25,-485-3p,-518d,-720) or sepsis only (miR-148a,-193a-5p,-199a-3p,-222,-25,-340,744). Bioinformatic analysis showed that when sepsis is associated with ARDS, those differentially expressed miRNAs potentially target messenger RNAs from the Glycoprotein VI/GP6 signaling pathway. Circulating EV-miRNA cargo could be potential biomarkers of lung inflammation during sepsis in patients requiring mechanical ventilation.</p>

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Circulating extracellular vesicles as potential biomarkers and mediators of acute respiratory distress syndrome in sepsis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月14日

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  • Marcelo Fernando do Nascimento,
  • Ludmila Rodrigues Pinto Ferreira,
  • José Mauro Vieira Junior,
  • Daniel Deheinzelin,
  • Ana Cláudia Aparecida Santos Nussbaum,
  • Luis Henrique Toshihiro Sakamoto,
  • Renata Ottes Vasconcelos,
  • Reinaldo Salomao,
  • Jaques Waisberg,
  • Luciano Cesar Pontes Azevedo,
  • Roger Chammas,
  • Juliana Monte Real

摘要

The early sequence of respiratory failure events after the onset of sepsis is still unknown. We hypothesize that the lung should signal through circulating extracellular vesicles (EVs) when it is affected by a systemic inflammatory response. Blood samples were obtained from septic patients with (n = 5) and without acute respiratory distress syndrome (ARDS) (n = 13) at 24 h of intensive care unit admission and 3 days later at Sírio-Libanês Hospital. Pulmonary-originated sepsis was not considered. The characteristics of the plasma-isolated EVs were compatible with exosomes. 48 miRNAs were evaluated by real-time PCR. Comparing all samples from patients with sepsis + ARDS to sepsis only, 9 miRNAs are transported in smaller amounts: miR-766 (-35.7, p = 0.002), miR-127 (-23.8, p = 0.001), miR-340 (-13.5, p = 0.006), miR-29b (-12.8, p = 0.001), miR-744 (-7.1, p = 0.05), miR-618 (-4.0, p = 0.02), miR-598 (-3.8, p = 0.035), miR-1260 (-2.5, p = 0.035); and miR-885-5p is expressed at higher levels (9.5; p = 0.028). In paired samples, the set of altered miRNAs is generally different (p < 0.05) between sepsis + ARDS (miR-1183,-1267,-1290,-17,-192,-199a-3p,-25,-485-3p,-518d,-720) or sepsis only (miR-148a,-193a-5p,-199a-3p,-222,-25,-340,744). Bioinformatic analysis showed that when sepsis is associated with ARDS, those differentially expressed miRNAs potentially target messenger RNAs from the Glycoprotein VI/GP6 signaling pathway. Circulating EV-miRNA cargo could be potential biomarkers of lung inflammation during sepsis in patients requiring mechanical ventilation.