Abstract: Oxidative stress plays an important role in cardio-vascular diseases and atherosclerosis. Fibrinogen (FB), plasma coagulation protein, is a risk factor of atherosclerosis. Importantly, it can be readily oxidized during oxidative stress and in pathological conditions. FB can promote angiogenesis by supporting migration and proliferation of endothelial cells. On the other hand, recent reports demonstrated cytotoxicity of oxidized fibrinogen (oxFB). Endothelial dysfunction plays a critical role in the atherosclerosis development, therefore it is important to understand the effect of oxFB on human endothelial cells (hEC), and the mechanism of the cell death. Here, we studied influence of oxFB on hEC during 24 h incubation in two conditions: (1) at low serum level (0.1%) and in the absence of growth factors ("starvation"); (2) in full medium (5% FBS) with growth factor supplement. Apoptosis was evaluated using analysis of nuclear morphology, phosphatidylserine externalization on hEC surface and caspase-3 activation. In starvation, we observed significant cell death via apoptosis. FB prevented starvation-induced cell death and caspase activation. Caspase activity in the presence of oxFB was 1.5 times higher as compared to FB, yet oxFB demonstrated significant cell protection during stress. Similarly, in optimal cultivation conditions FB decreased the rate of apoptosis by three times, while oxFB supported cell viability to the lesser extent. Thus, FB can protect hEC in stress conditions (in starvation); oxidative modification of FB diminishes its antiapoptotic properties.
Reference: Aseychev A.V., Azizova O.A., Scheglovitova O.N., Sklyankina N.N., Borisenko G.G., The influence of oxidized fibrinogen on apoptosis of endothelial cells, Biomeditsinskaya khimiya, 2011, vol: