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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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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Platelets synthesize large amounts of active plasminogen activator inhibitor 1
Helén Brogren,
Lena Karlsson,
Maria Andersson,
Lingwei Wang,
David Erlinge, and
Sverker Jern
From the Clinical Experimental Research Laboratory, Department of Medicine, Sahlgrenska University Hospital/Östra, Cardiovascular Institute, Göteborg, Sweden; and Department of Cardiology, Lund University Hospital, Lund, Sweden.
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 is inactive and therefore its role in clot stabilization is unclear. Because 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 polymerase chain reaction 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 enzyme-linked immunosorbent assay increased by 25% (P = .001). Metabolic radiolabeling with 35S-methionine followed by immunoprecipitation confirmed an ongoing 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 complexbind 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. (Blood. 2004;104:3943-3948)
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