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001-es BibID:BIBFORM121594
035-os BibID:(Scopus)85191442861
Első szerző:Krajcsir Bálint
Cím:Ponatinib Induces a Procoagulant Phenotype in Human Coronary Endothelial Cells via Inducing Apoptosis / Bálint Krajcsir, Marianna Pócsi, Zsolt Fejes, Béla Nagy Jr., János Kappelmayer, Ildikó Beke Debreceni
Dátum:2024
ISSN:1999-4923
Megjegyzések:BCR-ABL tyrosine kinase inhibitors (TKIs) are effective drugs in the treatment of patients with chronic myeloid leukemia. However, based on clinical studies, ponatinib was associated with the development of thrombotic complications. Since endothelial cells (ECs) regulate blood coagulation, their abnormal phenotype may play a role in the development of thrombotic events. We here aimed to investigate the effect of ponatinib on the procoagulant activity of cultured endothelial cells in vitro. Human coronary artery endothelial cells (HCAECs) were incubated with 50, 150, and 1000 nM of ponatinib. Subsequently, phosphatidylserine (PS) exposure and endothelial microvesicles (EMVs) were measured by flow cytometry. In addition, EC- and EMV-dependent thrombin generation was analyzed. To investigate pro-apoptotic effects of ponatinib, the level of Bax and Bcl-xL proteins were studied using Western blot and F3, THBD, and VCAM1 mRNAs were quantified by qPCR. Therapeutic concentrations of ponatinib significantly increased PS expression on ECs and the amount of EMVs which significantly shortened the time parameters of thrombin generation. In addition, these changes were associated with an increased ratio of Bax and Bcl-xL proteins in the presence of the decreased THBD mRNA level. Overall, ponatinib enhances the procoagulant activity of ECs via inducing apoptosis, which may contribute to thrombotic events.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
ponatinib therapy
endothelial cell
apoptosis
phosphatidylserine
endothelial microvesicles
thrombin generation
Megjelenés:Pharmaceutics. - 16 : 4 (2024), p. 1-14. -
További szerzők:Pócsi Marianna (1989-) (klinikai laboratóriumi kutató) Fejes Zsolt (1988-) (molekuláris biológus) Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos) Kappelmayer János (1960-) (laboratóriumi szakorvos) Bekéné Debreceni Ildikó (1970-) (biológus)
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