Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor for plasmin formation promoted by tissue and urokinase plasminogen activators. The present study demonstrates that thrombin increase PAI-1 antigen, biological activity, and gene expression in cultured baboon aortic smooth muscle cells (BASMC). Thrombin elevates PAI-1 antigen in conditioned medium of BASMC within 10 min of the treatment, with the peak increase after 30 min of the treatment. Overexpression of PAI-1 gene was detected in the cultures exposed to thrombin for at least 60 min. PAI activity in conditioned medium increased in the cultures treated with thrombin for at least 4 h. The thrombin-induced early increase of PAI-1 antigen (up to 30 min of the stimulation) was blocked by hirudin (a specific inhibitor of thrombin), mimicked by trypsin and not suppressed by cycloheximide (a protein synthesis inhibitor). The majority of metabolically labeled PAI-1 associated with BASMC was present in extracellular matrix. The level of extracellular matrix-associated PAI-1 was reduced 40% by 30 min of thrombin treatment. Our results suggest that thrombin not only increases PAI-1 transcription but also proteolytically cleaves PAI-1 from the extracellular matrix of vascular SMC. PAI-1 released by thrombin from the extracellular matrix may not alter PAI activity in extracellular fluid but may reduce the storage of PAI-1 in the extracellular matrix of vascular smooth muscle cells.
 ...
PMID:Effect of thrombin on release of plasminogen activator inhibitor-1 from cultured primate arterial smooth muscle cells. 774 May 4

To investigate the mechanism of atherogenesis and development of restenosis following angioplasty, the expression of t-PA in SMC at different intervals after the arterial injury was measured by morphological analysis, plasmin generation assay and in situ hybridization. t-PA activity of the iliac arteries was noticed to be significantly increased on the 4th day after injury, signalling the commencement of SMC migration from the media to intima, t-PA activity then decreased to approximately the normal level on the 7th day. Results from in situ hybridization also showed that the expression of t-PA mRNA in the intima and media increased significantly on the 4th day after the arterial injury, by the 7th day, t-PA mRNA was detected only in SMC located adjacent to the internal elastic lamina. These results suggest that t-PA might play an important role in SMC proliferation and migration following arterial injury.
 ...
PMID:[Expression of tissue-type plasminogen activator (t-PA) in smooth muscle cells of injured iliac arteries in rabbits]. 927 67

Smooth muscle cell migration plays a role in the development of intimal hyperplasia. Given the established role of the plasminogen activation system in cell migration, an approach to therapy is to overexpress an inhibitor of plasmin. Therefore, an adenoviral vector was constructed encoding the hybrid protein ATF.BPTI, which contains the active domain of bovine pancreas trypsin inhibitor (BPTI), fused to ATF, the amino terminal fragment or receptor-binding domain of u-PA. Adenoviral vectors expressing ATF and BPTI individually were also constructed, and a fourth vector was constructed encoding ATF.BPTI linked by an internal ribosomal entry site to Green Fluorescent Protein (ABIG). Both the expression and functionality of the recombinant proteins were established in human vascular smooth muscle cells. Adenoviral gene transfer of ATF.BPTI inhibited SMC migration more efficiently than the expression of ATF or BPTI individually. Expression of ABIG resulted in the co-expression of ATF.BPTI and Green Fluorescent Protein, thereby providing a tool to monitor transfection efficiency and the behavior of the transfected cells.
 ...
PMID:Adenoviral gene transfer of a u-PA receptor-binding plasmin inhibitor and green fluorescent protein: inhibition of migration and visualization of expression. 1101 72