Circulating microparticles from patients with septic shock exert protective role in vascular function

Hadj Ahmed Mostefai, Ferhat Meziani, Maria Letizia Mastronardi, Abdelali Agouni, Christophe Heymes, Cyrille Sargentini, Pierre Asfar, Maria Carmen Martinez, Ramaroson Andriantsitohaina

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

RATIONALE: Sepsis is an archetypal condition with molecular links between inflammation and coagulation. Both events can be orchestrated by the interaction between circulating and vascular cells that under activation release microparticles. OBJECTIVES: We characterized circulating microparticles from both nonseptic subjects and patients with septic shock and evaluated their contribution to vascular function. METHODS: Circulating microparticles and their cell origin were measured in blood from 36 patients with septic shock and 18 nonseptic subjects by flow cytometry. Microparticles were then injected intravenously into mice and vascular reactivity was assessed in aorta. Expression and activity of enzymes involved in nitric oxide (NO) and cyclooxygenase metabolite production were analyzed. MEASUREMENTS AND MAIN RESULTS: Circulating levels of microparticles and platelet- and endothelial-derived microparticles were increased in septic patients. Surprisingly, septic microparticles enhanced the sensitivity of contraction of mouse aorta in response to serotonin. Interestingly, septic microparticles enhanced the contraction of aorta from lipopolysaccharide-treated mice. This effect was linked neither to increased calcium entry nor to Rho kinase inhibitor-sensitive mechanisms. In addition, the effect of septic microparticles was not modified either by NO-synthase or cyclooxygenase-2 inhibitors, and was not associated with NO or O2- overproduction. The nonselective cyclooxygenase-2 inhibitor indomethacin reduced, and the specific thromboxane A2 antagonist SQ-29548 abolished, aortic contraction in mice treated with nonseptic and septic microparticles. The effect of septic microparticles was associated with increased thromboxane A2 production, and was sensitive to a selective thromboxane A2 antagonist. CONCLUSIONS: We provide evidence that increased circulating microparticles are protective against vascular hyporeactivity accounting for hypotension in patients with septic shock.
Original languageEnglish
Pages (from-to)1148-1155
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume178
Issue number11
Early online date21 Aug 2008
DOIs
Publication statusPublished - 1 Dec 2008

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Septic Shock
Thromboxane A2
Blood Vessels
Aorta
Cyclooxygenase 2 Inhibitors
Nitric Oxide
rho-Associated Kinases
Prostaglandin-Endoperoxide Synthases
Nitric Oxide Synthase
Indomethacin
Hypotension
Lipopolysaccharides
Serotonin
Sepsis
Flow Cytometry
Blood Platelets
Inflammation
Calcium
Enzymes

Keywords

  • Adult
  • Aged
  • Animals
  • Case-Control Studies
  • Cell-Derived Microparticles
  • Disease Models, Animal
  • Endothelium, Vascular
  • Female
  • Humans
  • Hypotension
  • Male
  • Mice
  • Middle Aged
  • Shock, Septic
  • Thromboxane A2
  • Vasoconstriction
  • Vasodilation
  • microvesicles
  • vasomotricity
  • cyclooxygenase
  • oxidative stress
  • sepsis

Cite this

Mostefai, H. A., Meziani, F., Mastronardi, M. L., Agouni, A., Heymes, C., Sargentini, C., ... Andriantsitohaina, R. (2008). Circulating microparticles from patients with septic shock exert protective role in vascular function. American Journal of Respiratory and Critical Care Medicine, 178(11), 1148-1155. https://doi.org/10.1164/rccm.200712-1835OC

Circulating microparticles from patients with septic shock exert protective role in vascular function. / Mostefai, Hadj Ahmed; Meziani, Ferhat; Mastronardi, Maria Letizia; Agouni, Abdelali; Heymes, Christophe; Sargentini, Cyrille; Asfar, Pierre; Martinez, Maria Carmen; Andriantsitohaina, Ramaroson.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 178, No. 11, 01.12.2008, p. 1148-1155.

Research output: Contribution to journalArticle

Mostefai, HA, Meziani, F, Mastronardi, ML, Agouni, A, Heymes, C, Sargentini, C, Asfar, P, Martinez, MC & Andriantsitohaina, R 2008, 'Circulating microparticles from patients with septic shock exert protective role in vascular function', American Journal of Respiratory and Critical Care Medicine, vol. 178, no. 11, pp. 1148-1155. https://doi.org/10.1164/rccm.200712-1835OC
Mostefai, Hadj Ahmed ; Meziani, Ferhat ; Mastronardi, Maria Letizia ; Agouni, Abdelali ; Heymes, Christophe ; Sargentini, Cyrille ; Asfar, Pierre ; Martinez, Maria Carmen ; Andriantsitohaina, Ramaroson. / Circulating microparticles from patients with septic shock exert protective role in vascular function. In: American Journal of Respiratory and Critical Care Medicine. 2008 ; Vol. 178, No. 11. pp. 1148-1155.
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AU - Mastronardi, Maria Letizia

AU - Agouni, Abdelali

AU - Heymes, Christophe

AU - Sargentini, Cyrille

AU - Asfar, Pierre

AU - Martinez, Maria Carmen

AU - Andriantsitohaina, Ramaroson

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AB - RATIONALE: Sepsis is an archetypal condition with molecular links between inflammation and coagulation. Both events can be orchestrated by the interaction between circulating and vascular cells that under activation release microparticles. OBJECTIVES: We characterized circulating microparticles from both nonseptic subjects and patients with septic shock and evaluated their contribution to vascular function. METHODS: Circulating microparticles and their cell origin were measured in blood from 36 patients with septic shock and 18 nonseptic subjects by flow cytometry. Microparticles were then injected intravenously into mice and vascular reactivity was assessed in aorta. Expression and activity of enzymes involved in nitric oxide (NO) and cyclooxygenase metabolite production were analyzed. MEASUREMENTS AND MAIN RESULTS: Circulating levels of microparticles and platelet- and endothelial-derived microparticles were increased in septic patients. Surprisingly, septic microparticles enhanced the sensitivity of contraction of mouse aorta in response to serotonin. Interestingly, septic microparticles enhanced the contraction of aorta from lipopolysaccharide-treated mice. This effect was linked neither to increased calcium entry nor to Rho kinase inhibitor-sensitive mechanisms. In addition, the effect of septic microparticles was not modified either by NO-synthase or cyclooxygenase-2 inhibitors, and was not associated with NO or O2- overproduction. The nonselective cyclooxygenase-2 inhibitor indomethacin reduced, and the specific thromboxane A2 antagonist SQ-29548 abolished, aortic contraction in mice treated with nonseptic and septic microparticles. The effect of septic microparticles was associated with increased thromboxane A2 production, and was sensitive to a selective thromboxane A2 antagonist. CONCLUSIONS: We provide evidence that increased circulating microparticles are protective against vascular hyporeactivity accounting for hypotension in patients with septic shock.

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