Nilotinib does not alter the secretory functions of carotid artery endothelial cells in a prothrombotic or antithrombotic fashion
| Autor: | Mehmet Ali Özcan, Şerife Solmaz, Omur Gokmen Sevindik, Güner Hayri Özsan, Özden Pişkin, Fatih Demirkan, Faize Yuksel, Aysun Adan Gökbulut, Abdullah Katgi, Yusuf Baran, Inci Alacacioglu |
|---|---|
| Přispěvatelé: | TR119193, Adan Gökbulut, Aysun, Baran, Yusuf, Izmir Institute of Technology. Molecular Biology and Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Cell viability Cell Survival Carotid arteries Endothelial cells Cardiovascular risk factors Nitric Oxide Nitric oxide chemistry.chemical_compound Internal medicine Antithrombotic medicine Humans In patient Function Potential mechanism Cells Cultured Cell Proliferation Dose-Response Relationship Drug business.industry Endothelial Cells Thrombosis Blood Proteins Hematology General Medicine medicine.disease Nilotinib Carotid Arteries Pyrimidines Endocrinology chemistry Cardiology business Carotid artery medicine.drug |
| Popis: | 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. Objectives: 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. Conclusion: 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|