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Updated: May 7, 2026
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Published on: March 22, 2024
Pharmacological modulation of procoagulant microparticles improves haemodynamic dysfunction during septic shock in
Julie Boisramé-Helms, Xavier Delabranche, Su-Emmanuelle Degirmenci
1Ferhat Meziani, MD, PhD, Service de Réanimation Médicale - Nouvel Hôpital Civil, 1, place de l'Hôpital, F-67091 Strasbourg cedex, France, Tel.: +33 369 550 434, Fax: +33 369 551 859,
Abstract:
Circulating microparticles play a pro-inflammatory and procoagulant detrimental role in the vascular dysfunction of septic shock. It was the objective of this study to investigate mechanisms by which a pharmacological modulation of microparticles could affect vascular dysfunction in a rat model of septic shock. Septic or sham rats were treated by activated protein C (aPC) and resuscitated during 4 hours. Their microparticles were harvested and inoculated to another set of healthy recipient rats. Haemodynamic parameters were monitored, circulating total procoagulant microparticles assessed by prothrombinase assay, and their cell origin characterised. Mesenteric resistance arteries, aorta and heart were harvested for western blotting analysis. We found that a) the amount and phenotype of circulating microparticles were altered in septic rats with an enhanced endothelial, leucocyte and platelet contribution; b) aPC treatment significantly reduced the generation of leucocyte microparticles and norepinephrine requirements to reach the mean arterial pressure target in septic rats; c) Microparticles from untreated septic rats, but not from aPC-treated ones, significantly reduced the healthy recipients' mean arterial pressure; d) Microparticle thromboxane content and aPC activity were significantly increased in aPC-treated septic rats. In inoculated naïve recipients, microparticles from aPC-treated septic rats prompted reduced NF-κB and cyclooxygenase-2 arterial activation, blunted the generation of pro-inflammatory iNOS and secondarily increased platelet and endothelial microparticles. In conclusion, in this septic shock model, increased circulating levels of procoagulant microparticles led to negative haemodynamic outcomes. Pharmacological treatment by aPC modified the cell origin and levels of circulating microparticles, thereby limiting vascular inflammation and favouring haemodynamic improvement.
Insights
Activated protein C (aPC) treatment in septic shock reduced harmful microparticles, improving vascular function and haemodynamics. This study shows aPC modulates microparticle origin and levels, limiting inflammation and haemodynamic decline.
Area of Science:
- Cardiovascular Biology
- Vascular Inflammation
- Sepsis Pathophysiology
Background:
- Circulating microparticles contribute to vascular dysfunction in septic shock.
- Their pro-inflammatory and procoagulant roles are detrimental.
Purpose of the Study:
- Investigate how pharmacological modulation of microparticles impacts vascular dysfunction in a rat model of septic shock.
- Assess the effects of activated protein C (aPC) on microparticle generation and function.
Main Methods:
- Septic and sham rats were treated with aPC and resuscitated.
- Microparticles were harvested and transferred to healthy recipients.
- Haemodynamic parameters, microparticle characteristics, and arterial activation markers were analyzed.
Main Results:
- Septic rats showed increased microparticles from endothelial, leukocyte, and platelet sources.
- aPC treatment reduced leukocyte microparticles and norepinephrine requirements.
- Microparticles from aPC-treated rats mitigated negative haemodynamic effects and reduced arterial inflammation in recipients.
Conclusions:
- Increased procoagulant microparticles in septic shock negatively impact haemodynamics.
- aPC treatment effectively modifies microparticle profiles, improving vascular inflammation and haemodynamic outcomes.
