Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growing evidence suggests that moderately elevated levels of homocysteine are associated not only with arterial thrombosis and atherosclerosis but also with venous thrombosis as well. We have reviewed recent studies that indicate that homocysteine inhibits several different anticoagulant mechanisms that are mediated by the vascular endothelium. The protein C enzyme system appears to be one of the most important anticoagulant pathways in the blood. Homocysteine inhibits the expression and activity of endothelial cell surface thrombomodulin, the thrombin cofactor responsible for protein C activation. Homocysteine inhibits the antithrombin III binding activity of endothelial heparan sulfate proteoglycan, thereby suppressing the anticoagulant effect of antithrombin III. Homocysteine also inhibits the ecto-ADPase activity of human umbilical vein endothelial cells (HUVECS). Because ADP is a potent platelet aggregatory agent, this action of homocysteine is prothrombotic. Homocysteine also interferes with the fibrinolytic properties of the endothelial surface because it inhibits the binding of tissue plasminogen activator. Homocysteine stimulates HUVEC tissue factor activity. We have found that lipoprotein(a) [Lp(a)] also stimulates HUVEC tissue factor activity. The combination of Lp(a) plus homocysteine induced more tissue factor activity than either agent alone. These disruptions in several different vessel wall-related anticoagulant functions provide plausable mechanisms for the occurrence of thrombosis in hyperhomocysteinemia.
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PMID:Homocysteine and hemostasis: pathogenic mechanisms predisposing to thrombosis. 864 72

Vascular endothelium is strategically located at the interface between tissue and blood. It is pivotal for protecting against vascular injury and maintaining blood fluidity. Normal endothelium releases prostacyclin and nitric oxide, potent inhibitors of platelet and monocyte activation and vasodilators. Their syntheses are governed by isoforms of enzymes. Normal endothelial surface expresses ecto-adenosine diphosphatase, which degrades adenosine diphosphate and inhibits platelet aggregation; thrombomodulin, which serves as a binding site for thrombin to activate protein C; and heparin-like molecules, which serve as a cofactor for antithrombin III. Normal endothelium secretes tissue plasminogen activator, which activates the fibrinolysis system. Endothelium produces and secretes von Willebrand factor, which mediates platelet adhesion and shear-stress-induced aggregation. Injury to endothelium is accompanied by loss of protective molecules and expression of adhesive molecules, procoagulant activities, and mitogenic factors, leading to development of thrombosis, smooth muscle cell migration, and proliferation and atherosclerosis.
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PMID:Role of endothelium in thrombosis and hemostasis. 871 85

Different clinical manifestations have been reported to occur in patients bitten by newborn and adult Bothrops jararaca snakes. Herein, we studied the chemical composition and biological activities of B. jararaca venoms and their immunoneutralization by commercial antivenin at these ontogenetic stages. Important differences in protein profiles were noticed both in SDS-PAGE and two-dimensional electrophoresis. Newborn venom showed lower proteolytic activity on collagen and fibrinogen, diminished hemorrhagic activity in mouse skin and hind paws, and lower edematogenic, ADPase and 5'-nucleotidase activities. However, newborn snake venom showed higher l-amino oxidase, hyaluronidase, platelet aggregating, procoagulant and protein C activating activities. The adult venom is more lethal to mice than the newborn venom. In vitro and in vivo immunoneutralization tests showed that commercial Bothrops sp antivenin is less effective at neutralizing newborn venoms. These findings indicate remarkable differences in biological activities of B. jararaca venom over its development. We suggest that not only venom from adult specimens, but also from specimens at other ontogenetic stages should be included in the venom pool used for raising antibodies. Thus, Bothrops antivenin can efficaciously neutralize proteins lacking in the adult venom pool, especially those that promote more intense hemostatic disturbances in victims of newborn snakes.
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PMID:Comparative analysis of newborn and adult Bothrops jararaca snake venoms. 2081 86