Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombotic thrombocytopenic purpura (TTP) is characterized by widespread occluding and persistent microthrombotic lesions. Evidence for both endothelial damage and primary platelet aggregation as possible pathogenetic mechanisms has been produced. Persistence of microthrombi has not been explained satisfactorily. In patients with TTP we studied plasma fibrinolysis and protein C. Tissue plasminogen activator (t-PA) activity levels, measured functionally, were low or unmeasurable in 11 of 12 patients; t-PA antigen levels, measured immunochemically, were normal in all six observed. The level of potent inhibitor of plasminogen activation directed against both t-PA and urokinase was elevated significantly in all 12, whereas the alpha 2-antiplasmin level was elevated in only two. Protein C antigen levels were low in three of six patients observed. Fibrinolysis levels in patients in remission did not differ from those in patients with acute disease. Plasma exchange resulted in temporary reversal of the abnormalities, but achievement of clinical remission was not associated with permanent normalization of fibrinolysis. Inasmuch as all 12 patients had severely depressed fibrinolytic mechanisms it is possible that a defect in the fibrin-clearing system permits thrombus formation to occur and proceed in an unchallenged fashion, thereby contributing to the complex events leading to arterial ischemia in vital organs.
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PMID:Fibrinolysis in health and disease: abnormal levels of plasminogen activator, plasminogen activator inhibitor, and protein C in thrombotic thrombocytopenic purpura. 243 36

Early signs of inflammatory demyelination include entry of fibrin(ogen) into the central nervous system (CNS), which is normally excluded by the blood-brain barrier, and up-regulation of components of the plasminogen activator system. Using mice deficient in tissue-type plasminogen activator (tPA-/-) and urokinase plasminogen activator receptor (uPAR-/-), we investigated the involvement of the PA system on the clinical and pathological features of experimental allergic encephalomyelitis, an animal model of multiple sclerosis. tPA-/- mice suffered an early and a more severe acute disease characterized by incomplete recovery when compared to wild-type controls, with significantly higher CNS levels of plasminogen activator inhibitor-1. This correlated with fibrin accumulation, which co-localized with nonphosphorylated neurofilament on thickened axons in experimental allergic encephalomyelitis tissue. In contrast, uPAR-/- mice had a delayed, less acute disease reflected in delayed infiltration of inflammatory cells. These animals developed chronic disease as a result of steadily increased inflammation, increased levels of urokinase-type plasminogen activator (uPA), and greater degree of demyelination. Thus, the plasminogen activator system can modulate both inflammatory and degenerative events in the CNS through the respective effects of tPA and uPAR on fibrinolysis and cell adhesion/migration, manipulation of which may have therapeutic implications for multiple sclerosis.
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PMID:A role for the plasminogen activator system in inflammation and neurodegeneration in the central nervous system during experimental allergic encephalomyelitis. 1604 38