Paul Arnold

Date of Award


Degree Type


Degree Name

Master of Science




Dr. Qingping Feng


Sepsis is a complex clinical syndrome that results from a harmful or damaging

host response to infection. Sepsis is characterized by the production of proinflammatory

cytokines like TNF-a and IL-ip, which have been shown to contribute to cardiovascular

dysfunction. Annexin A5 is a phospholipid binding protein that has been shown to have

anti-inflammatory, anti-apoptotic and anti-coagulant properties. However, its effect on

cardiac function during sepsis has not been established. This thesis investigated the

effect of annexin A5 on myocardial cytokine production and cardiac function during

endotoxemia in mice. It was found that annexin A5 treatment at the onset of

endotoxemia abrogated TNF-a and IL-1P production and prevented cardiac dysfunction.

Annexin A5 likely interacts with cell-surface receptor TLR4 to inhibit myocardial

cytokine expression to protect against cardiac dysfunction during endotoxemia. These

results suggest that annexin A5 provides a novel protective role in the heart during





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