Effect of nilotinib on coagulant functions of cultivated endothelial cells

INTRODUCTION: Chronic myeloid leukemia is a clonal myeloproliferative disorder caused by abnormally proliferating hematopoietic stem cell. CML is treated with tyrosine kinases, which blockes the effect of BCR-ABL1 chimeric protein already posess tyrosine kinase activity. Nilotinib is a second generation tyrosine kinase inhibitor which is synthetically derived from imatinib. There have been concerns about the possible prothrombotic effect of nilotinib especially on the patients with cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. We aimed to evaluate the potential harmful effect or effects of nilotinib on the endothelial cells and their functions.MATERIAL and METHODS: In this study, we aimed to assess the viability and secretory functions of carotid endothelial cells which were cultivated with Nilotinib. In order to assess the endothelial function, NO, von Willebrand Factor, tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) and endothelin 1 (secreted from endothelial cells) levels were evaluated.RESULTS: Nilotinib increased the secretion of t-PA, NO, PAI-1, vWF and ET-1 when compared with nilotinib naive cells in a dose and duration dependent manner.CONCLUSION: It cannot be explicitly concluded that nilotinib effects the endothelial cell functions in a pro-thrombotic or anti-thrombotic fashion from the results of this study. While suppressing the viability of endothelial cells nilotinib may cause delayed restoration of endothelial damage and may indirectly plays a role in vascular events. In addition the results obtained from this in-vitro designed study may not correctly reflect the in-vivo affect of the drug. We may finally conclude that our study is a preliminary pilot study trying to extablish the effect of nilotinib on carotid artery endothelial cells. Some further studies may clarify the possible pathogenetic mechanisms involved in the prothromboticprocess caused by nilotinib and may induce therapeutic approaches to decrease the incidence of this harmful side effect.