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Thromb Haemost 2001; 85(06): 1086-1089
DOI: 10.1055/s-0037-1615968
Review Article
Schattauer GmbH

Regulation of PAI-1 Concentration in Platelets by Systemic Administration of Antisense Oligonucleotides to Rats

Zofia Pawlowska
1   Department of Biophysics, Medical University in Lodz, Lodz, Poland
,
Ewa Chabielska
2   Department of Pharmacodynamics, Medical University in Bialystok, Lodz, Poland
,
Anna Kobylanska
3   Department of Bioorganic Chemistry of the Center for Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland
,
Anna Maciaszek
3   Department of Bioorganic Chemistry of the Center for Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland
,
Maria Swiatkowska
1   Department of Biophysics, Medical University in Lodz, Lodz, Poland
,
Wlodzimierz Buczko
2   Department of Pharmacodynamics, Medical University in Bialystok, Lodz, Poland
,
Wojciech J. Stec
3   Department of Bioorganic Chemistry of the Center for Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland
,
Czeslaw S. Cierniewski
1   Department of Biophysics, Medical University in Lodz, Lodz, Poland
› Author Affiliations
Further Information

Publication History

Received 18 April 2000

Accepted after resubmission 31 January 2001

Publication Date:
12 December 2017 (online)

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Summary

In this report we tested the effect of oligodeoxyribonucleotides antisense to PAI-1 mRNA administered into rats on PAI-1 concentration in platelets. Low doses of the antisense oligonucleotide (MPO-16R) reduced PAI-1 activity, both in rat blood plasma and platelet lysates by 20.5% and 28.7%, respectively. There was no change in platelet count after treatment with MPO-16R but treated platelets showed lower aggregability as compared with controls (37 ± 13% and 54 ± 12%, respectively). In an experimental model of rat arterial thrombosis, low doses of MPO-16R caused a significant delay in the occlusion time (31.8%). These data further support for the role of PAI-1 as a major determinant of arterial thrombolysis resistance and for the first time demonstrate the possibility of reduction of platelet PAI-1 concentration by antisense approach.

Key words

PAI-1 - antisense oligonucleotides - blood platelets
 

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