Horman, Sandrinede Cartier d'Yves, EmmaEmmade Cartier d'Yves2025-05-142025-05-142025-05-142022https://hdl.handle.net/2078.2/27619According to the World Health Organization, sepsis causes one in five deaths worldwide. However, the mechanisms involved in its pathophysiology remain unclear and a source of active scientific research. Platelets play an important role in sepsis as this syndrome is characterized by coagulopathy. In addition to their involvement in hemostatic mechanisms, platelets impact the inflammatory state of patients by producing lipid mediators of inflammation. Previous work from our laboratory has shown that acetyl-CoA carboxylase (ACC), responsible for de novo platelet lipid synthesis, is phosphorylated and thus inhibited by AMP-activated protein kinase (AMPK) in response to thrombin stimulation. Since hypercoagulation in septic patients is associated with high thrombin production, we hypothesised that ACC would be more phosphorylated in their platelets. This work is therefore part of a clinical project which aims to test the hypothesis that platelet ACC, by modulating the profile of platelet and/or circulating lipids, could influence the thrombo-inflammatory response of septic patients (PLACCSEPS: Prospective evaluation of PLatelets Acetyl-CoA Carboxylase phosphorylation state in SEPtic Shock patients). The results obtained show significant variations in platelet ACC expression and phosphorylation during sepsis. These data were confirmed in an experimental model of endotoxemia. Lipidomic analysis of human and murine platelets shows that septic shock induces a decrease in phosphatidylcholines and phosphatidylethanolamines containing long polyunsaturated fatty acid chains (ω3 and ω6), key phospholipids for the generation of pro- and anti-inflammatory lipid mediators. Our preliminary data, obtained in humans and mice, suggest that elevated ACC phosphorylation is associated with higher content of these phospholipids as well as reduced endothelial and platelet activation, coagulation and inflammation (mainly myeloid).Sepsis Plaquettes Lipides Inflammation Acetyl-coA Carboxylasetext::thesis::master thesisthesis:35935