Regulation of plasminogen activator inhibitor activity in endothelial cells by tissue-type plasminogen activator

G. Y. Shi, C. C. Hsu, B. I. Chang, C. F. Tsai, H. S. Han, M. D. Lai, M. T. Lin, W. C. Chang, L. Y C Wing, C. J. Jen, M. J. Tang, H. L. Wu

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Abstract

Tissue-type plasminogen activator (t-PA) may stimulate the expression of plasminogen activator inhibitor type 1 (PAI-1) mRNA in cultured human umbilical vein endothelial cells. The PAI-1 antigen in the conditioned medium of cells, pretreated with t-PA, was less than the control, probably due to the formation and degradation of the t-PA-PAI-1 complex. However, the PAI activity of the t-PA-pretreated cells reached the same level as control group, 24 h after the residual t-PA activity was rapidly neutralized by the newly synthesized PAI-1. To test the release of PAI-1 from the substratum of the endothelial cells, the cultured cells were metabolically prelabeled with 35S-methionine for 3 h and then treated with t-PA. The 35S-PAI-1 of 46 kDa was found in the substratum and culture medium of cultured endothelial cells as analyzed by the SDS-PAGE after immunoprecipitation. During the treatment of endothelial cells with t-PA, the PAI-1 of 46 kDa in the cell substratum disappeared, and the 110 kDa t-PA-PAI-1 complex, the 81 kDa degraded t-PA-PAI-1, and the 44 kDa degraded PAI-1 products concomitantly appeared in the conditioned medium instead. In summary, t-PA can regulate the fibrinolytic activity of endothelial cells by enhancing PAI-1 mRNA biosynthesis and release PAI-1 from the substratum to neutralize t-PA activity. The PAI-1 which released into the medium was immediately converted to the inactive latent form in the absence of active t-PA.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalFibrinolysis
Volume10
Issue number3
Publication statusPublished - 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

Cite this

Shi, G. Y., Hsu, C. C., Chang, B. I., Tsai, C. F., Han, H. S., Lai, M. D., Lin, M. T., Chang, W. C., Wing, L. Y. C., Jen, C. J., Tang, M. J., & Wu, H. L. (1996). Regulation of plasminogen activator inhibitor activity in endothelial cells by tissue-type plasminogen activator. Fibrinolysis, 10(3), 183-191.