Glycolytic reprogramming fuels myeloid cell-driven hypercoagulability

Area of Science:

• Immunometabolism
• Hematology
• Inflammatory Diseases

Background:

• Myeloid cell metabolic reprogramming is key in inflammatory diseases.
• The role of this reprogramming in inflammation-induced hypercoagulability remains unclear.

Purpose of the Study:

• To investigate the role of inflammation-associated metabolic reprogramming in regulating blood coagulation.
• To explore the link between myeloid cell metabolism and hypercoagulability.

Main Methods:

• Utilized novel myeloid cell-based global hemostasis assays.
• Employed murine models of immunometabolic disease, including high-fat diet-induced obesity and colitis.

Main Results:

• Glycolysis fuels myeloid cell tissue factor expression, increasing thrombin generation during inflammation.
• Inhibition of glycolysis boosts macrophage fibrinolytic activity.
• Macrophage activation enhances endothelial protein C receptor (EPCR) expression, promoting protein C activation.
• EPCR expression on tissue-resident macrophages and adipose tissue macrophages from obese mice was elevated.
• EPCR-positive myeloid cells infiltrated inflamed colonic tissue in colitis models.

Conclusions:

• Immunometabolic regulation of myeloid cell hypercoagulability is identified.
• This study opens therapeutic avenues for mitigating thromboinflammatory diseases.