PLEIOTROPIC EFFECTS OF ORAL ANTICOAGULANTS

In this paper, we present a literature review with the purpose of elucidating the pleiotropic effects of oral anticoagulants. The literature search was performed using the PubMed and SCOPUS databases. Pleiotropic effects of direct anticoagulants are determined by the interaction of Xa and thrombin IIa factors with PAR-1 and PAR-2 receptors. The focus of this review is the connection between oral anticoagulants and their effects on atherosclerosis, angiogenesis, inflammation, cardiac remodelling, oncogenesis and glomerular diseases. Direct anticoagulants exhibit an anti-atherosclerotic effect manifested in a decreased progression and destabilization of atherosclerotic lesions. This effect is confirmed by a decreased binding activity of DNA with NF-kB and AP-1 transcription factors and reduced levels of some mediators. Such effects of new oral anticoagulants also relate to the processes of cardiac remodelling. FXa inhibitors contribute to the prevention of cardiac remodelling by reducing the processes of inflammation and fibrosis, which are associated with a decrease in the expression of PAR receptors in the heart. A number of studies also demonstrate an anti-inflammatory effect of oral anticoagulants, which is confirmed by reduced expression of mRNA inflammatory cytokines under the influence of direct anticoagulants and the production of IL-6 under the influence of warfarin. FXa inhibitors are shown to increase the expression of vascular growth factors, stimulate the migration of еndothelial рrogenitor сells and improve their function, thus manifesting their angiogenic pleiotropic effect. In addition, warfarin has an impact both on angiogenesis by means of reducing the activation of Axl tyrosine kinases and on glomerular pathologies by means of affecting the proliferation of mesangial cells through the Gas6/Axl pathway. The antitumour activity of warfarin is associated with inhibition of Gas6-mediated activation of Axl on tumour cells. Further investigations are required to fully understand the effect of oral anticoagulants on haemostasis.