Regulation of PAI-1 concentration in platelets by systemic administration of antisense oligonucleotides to rats.
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.
Pawlowska
Z
Z
Department of Biophysics, Medical University in Lodz, Poland.
Chabielska
E
E
Kobylanska
A
A
Maciaszek
A
A
Swiatkowska
M
M
Buczko
W
W
Stec
W J
WJ
Cierniewski
C S
CS
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D020320:Oligoribonucleotides, Antisense / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control
D020320:Oligoribonucleotides, Antisense; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger