HEPARIN COFACTOR II/GLYCOSAMINOQLYCAN INTERACTIONS

点击翻译按钮获取中文摘要

Heparin cofactor II (HCII) is a glycoprotein in human plasma that inhibits thrombin rapidly in the presence of heparin or dermatan sulfate. In contract to antithrombin III (ATIII), HCII does not inhibit factor Xa or other coagulation proteases. Although heparin increases the activity of both HCII and ATIII, dermatan sulfate specifically activates HCII. HCII activity is decreased in many patients with disseminated intravascular coagulation and peatic failure but is normal in patients with thrombosis. The following studies will be done to better understand the specific interactions between HCII, thrombin, and glycosaminoglycans: (1) determination of the structure of the HCII-binding region of heparin and comparison of this structure to the high-affinity ATIII-binding ogliosaccharide; (3) identification of types of cells that activate HCII and characterization of the active cellular proteoglycans; (4) determination of dissociation constants for oligosaccharide binding to HCII; (5) determination of the amino acide sequence of the reactive site of HCII; and (6) measurement of HCII activity and thrombin-HCII complex in various patients. These studies may provide clues to the physiological functions of HCII as well as a basis for the potential therapeutic use of dermatan sulfate as an anticoagulant.