Regulation of fibrinolysis by annexin II tetramer

The antiphospholipid syndrome is a systemic autoimmune disorder which affects endothelial cells and results in a combination of arterial and/or venous thrombosis and recurrent fetal loss. Recent studies have suggested that that the pathogenic antibodies may be directed against a complex of beta2glycoprotein I and AIIt. We propose to establish if AIIt plays a key role in this disease. We will also examine why the clustering of the beta2glycoprotein I-AIIt complex by these antibodies so dramatically affects endothelial cell properties. One of the key functions of endothelial cells is to maintain blood fluidity by promoting the fibrinolytic state. We are also investigating the possibility that endothelial cell surface AIIt may also be an important regulator of fibrinolysis by promoting formation of the key fibrinolytic enzyme, plasmin