720 Natural anticoagulant/anti-inflammatory mechanisms
Wednesday November 18, 2015 from 09:00 to 10:30
Plenary Room 1

Charles Esmon, United States

Member and Head

Coagulation Biology Laboratory

Oklahoma Medical Research Foundation

Recommended Reading Websites
Xu et al Nature Medicine 15:1318-1321, 2009.

Huang et al Hepatology 54(3):999-1008, 2011.


Natural anticoagulant/anti-inflammatory mechanisms

Charles Esmon1.

1Coagulation Biology Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States

Activated protein C has been shown to reduce complications in a variety of disease models including sepsis, diabetes, inflammatory bowel disease, asthma and stroke. Thrombomodulin is involved not only in protein C activation but in down regulating complement activation. Mutations in thrombomodulin have been identified that eliminate its ability to inhibit complement activation. Patients with these mutations appear to be susceptible to atypical hemolytic uremic syndrome, the onset of which is often linked to some inflammatory stimulus. The endothelial protein C receptor (EPCR) is involved in binding protein C and increasing protein C activation rates. It also binds activated protein C and that complex enhances endothelial barrier function and decreases elaboration of adhesion molecules on endothelium, processes that involve activation of protease activated receptors.   EPCR also serves as a binding site for malaria infected red cells.  This interaction appears to contribute to stroke in infected children.  In many inflammatory diseases, cells release DNA histone complexes. The histones activate toll like receptors 2, 4 and 9 thereby triggering an inflammatory response. The histones contribute to organ transplant injury, acetaminophen toxicity, sepsis, lung injury, radiation injury, ischemic stroke and most likely trauma induced organ injury. Activated protein C can cleave the most active histones and thereby block their pro-inflammatory activity. Thus, the pathway serves many functions in modulating inflammatory diseases.

Lectures by Charles Esmon

When Session Talk Title Room
09:00 - 10:30
Controlling Inflammation & Coagulation Natural anticoagulant/anti-inflammatory mechanisms Plenary Room 1

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