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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3943-3948.
Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-04-1439.
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Submitted April 16, 2004
Accepted July 29, 2004
Platelets synthesize large amounts of active plasminogen activator inhibitor-1
Helen Brogren, Lena Karlsson, Maria Andersson, Lingwei Wang, David Erlinge, and Sverker Jern*
Department of Medicine, Sahlgrenska University Hospital/Ostra, Cardiovascular Institute, Clinical Experimental Research Laboratory, Goteborg, Sweden
Lund University Hospital, Department of Cardiology, Lund, Sweden
* Corresponding author; email: sverker.jern{at}hjl.gu.se.
Previous studies have suggested that plasminogen activator inhibitor 1 (PAI-1) released from platelets convey resistance of platelet-rich blood clots to thrombolysis. However, the majority of PAI-1 in platelets has been shown to be inactive and therefore its role in clot stabilization is unclear. Since platelets retain mRNA and capacity for synthesis of some proteins, we investigated if platelets can de novo synthesize PAI-1 with an active configuration. PAI-1 mRNA was quantified with real-time PCR and considerable amounts of PAI-1 mRNA were detected in all platelet samples. Over 24 hours, the amount of PAI-1 protein as determined by an ELISA increased by 25% (p=0.001). Metabolic radiolabeling with 35S-methionine followed by immunoprecipitation confirmed an on-going PAI-1 synthesis, which could be further stimulated by thrombin and inhibited by puromycin. The activity of the newly formed PAI-1 was investigated by incubating platelets in the presence of tissue-type plasminogen activator (tPA). This functional assay showed that the majority of the new protein was in an active configuration and could complex-bind tPA. Thus, there is a continuous production of large amounts of active PAI-1 in platelets, which could be a mechanism by which platelets contribute to stabilization of blood clots.
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