Abstract 363: Thrombin Activatable Fibrinolysis Inhibitor is a Regulator of Angiogenic Potential in Endothelial Cells

Angiogenesis, the sprouting of new blood vessels from existing vessels, is a process that is fundamental to both normal physiology, as well as disease processes such as atherosclerosis and cancer metastasis. A key regulator of the angiogenesis is the elaboration of pericellular proteolytic activity including plasmin and the matrix metalloproteases (MMPs). Thrombin activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen that can be cleaved by thrombin, plasmin, or thrombin in complex with thrombomodulin (TM) to form activated TAFI (TAFIa). TAFIa cleaves carboxyl terminal lysine and arginine residues from substrates, including plasminogen-binding sites on cell surface receptors. TAFIa is thus a regulator of pericellular plasminogen activation. Plasmin regulates angiogenesis through MMP activation and degradation of the extracellular matrix (ECM). Previous studies have shown that TAFIa downregulates endothelial tube formation in a fibrin matrix, likely through inhibition of fibrin degradation. The curr...