Proteome analysis of irradiated endothelial cells reveals persistent alteration of RhoGDI and NO signalling pathways

Background: Recent epidemiological studies indicate that radiation doses as low as 0.5 Gy may increase the risk of cardiovascular disease. The aim of the present study was to investigate whether this radiation dose causes molecular alterations in endothelial cells that could support the suspicion of low-dose cardiovascular risk raised by population studies.
Materials and Methods: Radiation-induced changes in the proteome of human coronary artery endothelial cell line were analysed using triplex isotope-coded protein labelling technology combined with LC–ESI–MS/MS. The cells were irradiated using the dose of 0.5 Gy (X-ray) and investigated after different time intervals (1 day, 1 week, 2 weeks). The proteomics and bioinformatics data were validated by immunoblotting and ELISA.
Results: The radiation-induced alteration of the endothelial proteome was characterised by perturbation of RhoGDI and NO signalling pathways. This was accompanied with reduced proteasome activity and enhanced protein carbonylation indicating augmented oxidative stress.
Conclusions: The persistent adverse molecular changes found in this study are indicative of endothelial dysfunction and support the epidemiological data showing significantly increased risk of cardiovascular disease at 0.5 Gy.