Anticoagulant effects of an antidiabetic drug on monocytes in vitro.

Abstract:

INTRODUCTION:Monocyte- and microparticle (MP)-associated tissue factor (TF) is upregulated in diabetes. Lipopolysaccharide (LPS) induces expression of TF and alternatively spliced TF (asTF) and increases MP release from monocytes. Using LPS-stimulated TF-bearing human monocytes, we examined whether glibenclamide, a sulfonylurea used to treat diabetes type 2, might possess anticoagulant properties. METHODS:We studied the effects of glibenclamide on cell- and supernatant-associated procoagulant activity (Factor Xa-generating assay and clot formation assay), on expression of TF and asTF (flow cytometry, RT-qPCR, western blot) and on cell viability and MP release (flow cytometry). RESULTS:Glibenclamide dose-dependently decreased procoagulant activity of cells and supernatants. The reduction in cellular procoagulant activity coincided with reduced expression of TF and asTF in cells, whereas cell viability remained almost unchanged. The glibenclamide-induced reduction in procoagulant activity of supernatants appeared to be associated with a decreased number of released MPs. CONCLUSIONS:Reduction of monocyte- and supernatant-associated procoagulant activity by glibenclamide is associated with decreased expression of TF and asTF and possibly with a reduced MP number. Our data indicate that glibenclamide reduces the prothrombotic state in LPS-stimulated monocytes in vitro. Glibenclamide might therefore also have an anticoagulant effect in vivo, but this needs to be further evaluated.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Henriksson CE,Hellum M,Haug KB,Aass HC,Joø GB,Øvstebø R,Trøseid AM,Klingenberg O,Kierulf P

doi

10.1016/j.thromres.2011.07.007

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

e100-6

issue

5

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(11)00353-7

journal_volume

128

pub_type

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