Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral contraceptives caused increased fibrinogen, FVII, FX, and fibrinolysis. The latter was associated with elevated FXII and PKK, while C1-INH was decreased, ATIII and alpha 2M were unchanged; it could not be accounted for by changes in t-PA, u-PA, PAI, plasminogen, alpha 2-AP, proteins C or S. HCII and alpha 1-PI were increased and may regulate the availability of thrombin and FXIa. The increased FXII/PKK dependent fibrinolytic potential and HCII may offset any increase in thrombin generation, while alpha 1-PI limits intrinsic coagulation.
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PMID:Procoagulant changes induced by oral contraceptives are balanced by an increased fibrinolytic tendency. 146 38

A series of coagulation tests is described by which an increased thrombotic tendency is likely to be detected. These tests were carried out in 268 patients with venous thromboembolic disease and in 583 patients with arterial thrombotic manifestations. In venous thromboembolism alterations which point to hypercoagulability were found in 50% of all cases. Most frequent findings were a diminished availability of t-PA followed by low levels of Protein C, AT III and of Heparin cofactor II. In arterial thrombotic disease alterations of the clotting system were found in 77% of the patients. There was a high frequency of increased spontaneous platelet aggregation, of a diminished t-PA availability and of a combination of both alterations. Other abnormal results were rare with the exception of a diminished Heparin cofactor II which was found in 3% of the patients. The consequences which arise for prophylaxis and therapy when the defect is known are discussed.
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PMID:New diagnostic possibilities for the detection of thrombophilic states. 246 11

Hemovasal produced by Manetti-Roberts, Florence, Italy, is a glycosaminoglycan obtained from porcine intestinal mucosa which belongs to the family of heparan sulfates. The substance was examined On 36 male survivors of myocardial infarction with an interval of at least 6 months after the acute event. No anticoagulants were given and ASA was withdrawn at least 2 weeks before the trial. Hemovasal was administered in 3 different i.m. doses as single injections. A further group received a daily oral dose of 300 mg for one week. A comparable placebo group of patients as well as a group of healthy volunteers was run in parallel. The coagulation profile showed only a slight prolongation of the aPTT, a trace of diminution of Antithrombin III and no activation of Heparin cofactor II. The fibrinolytic system showed an enhancement of the diurnal increase of t-PA without an alteration of the total increase of this activity. There was a considerable and highly significant diminution of the PAI-1 activity. This was dose dependent and could be found after i.m. as well as after oral administration. It was assumed that the thrombolytic effect which was repeatedly described was a consequence of the diminution of PAI-1.
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PMID:On the action of a heparan-like glycosaminoglycan (Hemovasal) on the mechanism of haemostasis and fibrinolysis. 763 1

Heparin cofactor II functions as a physiological inhibitor of thrombin activity. The rate of inactivation of thrombin by heparin cofactor II is increased in the presence of dermatan sulfate, which is produced by fibroblasts or smooth muscle cells. To elucidate the role of heparin cofactor II in the extravascular cells, we induced expression of heparin cofactor II in cultured human fibroblasts or vascular smooth muscle cells using adenovirus-mediated gene transfer. After infection of adenovirus vector, these cells secreted heparin cofactor II protein into culture medium. The expressed heparin cofactor II formed the complex with exogenous thrombin and inhibited the proteolytic activity of thrombin. Expression of heparin cofactor II by infection of adenovirus vector inhibited thrombin-induced tissue-type plasminogen activator and interleukin-6 releases from fibroblasts and thrombin-induced interleukin-6 release from vascular smooth muscle cells. These findings show that fibroblasts and vascular smooth muscle cells expressing heparin cofactor II are resistant to thrombin-induced cellular responses.
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PMID:Adenovirus-mediated expression of heparin cofactor II inhibits thrombin-induced cellular responses in fibroblasts and vascular smooth muscle cells. 1603 21