As a cell surface tissue plasminogen activator (tPA)-plasminogen receptor, the annexin A2 (A2) complex facilitates plasmin generation on the endothelial cell surface, and is an established regulator of hemostasis. Whereas A2 is overexpressed in hemorrhagic disease such as acute promyelocytic leukemia, its underexpression or impairment may result in thrombosis, as in antiphospholipid syndrome, venous thromboembolism, or atherosclerosis. Within immune response cells, A2 orchestrates membrane repair, vesicle fusion, and cytoskeletal organization, thus playing a critical role in inflammatory response and tissue injury. Dysregulation of A2 is evident in multiple human disorders, and may contribute to the pathogenesis of various inflammatory disorders. The fibrinolytic system, moreover, is central to wound healing through its ability to remodel the provisional matrix and promote angiogenesis. A2 dysfunction may also promote tissue fibrogenesis and end-organ fibrosis.
Keywords: angiogenesis; annexin A2; autoimmune disease; fibrinolysis; fibrosis; inflammation; thrombosis; tissue repair.