Anticoagulant effects of an antidiabetic drug on monocytes in vitro |
| |
Authors: | Henriksson C E Hellum M Haug K B F Aass H C Joø G B Øvstebø R Trøseid A M Klingenberg O Kierulf P |
| |
Affiliation: | a Blood cell research group, Section for research, Department of Medical Biochemistry, Oslo University Hospital, Ullevaal, Oslo, Norwayb Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway |
| |
Abstract: | IntroductionMonocyte- 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.MethodsWe 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).ResultsGlibenclamide 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.ConclusionsReduction 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. |
| |
Keywords: | MP, Microparticle TF, Tissue Factor asTF, alternatively spliced Tissue Factor LPS, Lipopolysacharride PS, Phosphatidylserine RBC, Red blood cells ABC, ATP-binding cassette SUR, Sulfonylurea receptor mAb, monoclonal antibody Ann V, Annexin V 7-AAD, 7-amino-actinomycin D PE, Phycoerythrin FITC, Fluorescein isothiocyanate TFPI, Tissue Factor Pathway Inhibitor |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|