Annexin A5 Inhibits Myocardial Inflammation and Improves Cardiac Function during Endotoxemia in Mice

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 t endotoxemia