Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent observation that knock-out of protease-activated receptor-4 (PAR4) ablates thrombin signaling in mouse platelets and protects against ferric chloride-induced thrombosis of mouse mesenteric arterioles suggests that thrombin's actions on platelets can play an important role in thrombosis. Complete ablation of thrombin signaling would be difficult to achieve in human beings because human platelets have 2 thrombin receptors that are each capable of mediating transmembrane signaling. However, it is possible that complete ablation of thrombin signaling in platelets is not necessary for an antithrombotic effect. In mouse platelets, PAR3 functions as a cofactor that binds thrombin and promotes productive cleavage of PAR4, and thrombin responses are decreased but not absent in Par3(-/-) platelets. We now report that Par3(-/-) mice were protected against ferric chloride-induced thrombosis of mesenteric arterioles and against thromboplastin-induced pulmonary embolism. Surprisingly, Par3(-/-) and Par4(-/-) mice showed similar degrees of protection in these models and similar prolongation of tail bleeding times. Thus, even a partial decrease in mouse platelet responsiveness to thrombin protected against thrombosis and impaired hemostasis in some settings. These results demonstrate the importance of PAR3's unusual cofactor function and underscore the relative importance of thrombin's actions on platelets in vivo. They also suggest that PAR inhibition might be explored for the prevention or treatment of thrombosis in human beings.
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PMID:Protection against thrombosis in mice lacking PAR3. 1238 23

The fibrinolytic function of endothelial cells plays an important role in the pathophysiology of pulmonary vascular diseases. In this study, the effects of pro-urokinase, a new thrombolytic drug that is currently being tested for the treatment of pulmonary embolism, on the expression of urokinase-type plasminogen activator (u-PA) and u-PA receptor (u-PAR) were assessed. The role of u-PAR was also investigated. Immunocytofluorescence and RT-PCR techniques were employed. In normal human pulmonary arterial endothelial cells (HPAECs), the expression levels of u-PA and u-PAR were very low. Incubation with pro-urokinase up-regulated u-PA expression at both the mRNA level and the protein level; however, the expression of u-PAR was not affected. The effect of pro-urokinase induction was totally inhibited by the release of u-PAR from the HPAECs' surface with PLC. This result suggests that the combination of u-PA with u-PAR may be a critical pathway for the induction of u-PA expression.
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PMID:Pro-urokinase up-regulates the expression of urokinase-type plasminogen activator (u-PA) in human pulmonary arterial endothelial cells. 1764 Jul 19