title: Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion.
abstract: BACKGROUND
  There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear.
  
  
  OBJECTIVE
  In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib.
  
  
  METHODS
  3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants.
  
  
  RESULTS
  There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells.
  
  
  CONCLUSIONS
  Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability.
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Katgı
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey omurgok17@hotmail.com.
authors.forename: Ömür Gökmen
authors.initials: ÖG
authors.lastname: Sevindik
authors.affiliation: Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey.
authors.forename: Aysun Adan
authors.initials: AA
authors.lastname: Gökbulut
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Güner Hayri
authors.initials: GH
authors.lastname: Özsan
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Faize
authors.initials: F
authors.lastname: Yüksel
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Şerife Medeni
authors.initials: ŞM
authors.lastname: Solmaz
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: İnci
authors.initials: İ
authors.lastname: Alacacıoğlu
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Özcan
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Demirkan
authors.affiliation: Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Baran
authors.affiliation: Department of Hematology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Özden
authors.initials: Ö
authors.lastname: Pişkin
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D013927:Thrombosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D001798:Blood Proteins; D011743:Pyrimidines; D009569:Nitric Oxide; C498826:nilotinib
keywords: carotid artery; cell viability; endothelial cells; function; nilotinib