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Updated: Jul 2, 2026
Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Circulating microparticles from patients with septic shock exert protective role in vascular function
Hadj Ahmed Mostefai1, Ferhat Meziani, Maria Letizia Mastronardi
1INSERM U771, CNRS UMR 6214, and Université d'Angers, France.
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.
Insights
Increased microparticles in septic shock patients enhance aortic contraction via thromboxane A2, suggesting a protective role against vascular hyporeactivity and hypotension.
Area of Science:
- Cardiovascular Research
- Inflammation and Immunology
- Sepsis Pathophysiology
Background:
- Sepsis involves complex interactions between inflammation and coagulation.
- Activated circulating and vascular cells release microparticles, key mediators in sepsis.
Purpose of the Study:
- Characterize circulating microparticles in septic shock patients versus nonseptic individuals.
- Evaluate the impact of these microparticles on vascular function.
Main Methods:
- Flow cytometry analyzed microparticles and their cellular origins in septic shock patients and controls.
- Microparticles were administered to mice to assess aortic vascular reactivity.
- Enzyme activity related to nitric oxide (NO) and cyclooxygenase pathways was analyzed.
Main Results:
- Septic shock patients exhibited elevated levels of circulating microparticles, particularly those derived from platelets and endothelial cells.
- Septic microparticles paradoxically enhanced aortic contraction sensitivity to serotonin in mice.
- This effect was mediated by increased thromboxane A2 production, not by NO or calcium signaling pathways.
Conclusions:
- Elevated circulating microparticles in sepsis are associated with enhanced thromboxane A2 production.
- These microparticles appear to counteract vascular hyporeactivity, potentially protecting against septic shock-induced hypotension.
