The role of the proteasome in endothelial cell senescence

Endothelial cells undergo senescence in vitro and in vivo, which contributes to endothelial dysfunction and vascular diseases. Senescence may result from continuous cell division and mitotic exhaustion, known as replicative senescence or by cellular pathways responsive to stress especially in certain inflammatory or oxidative microenvironments. A decline in protein degradative systems leading to the accumulation of protein aggregates is suggested to represent one major factor driving cellular senescence during ageing. The current project was aimed at characterising proteasomal protein degradation in endothelial cells undergoing replicative or premature senescence or chronological ageing in mice and to investigate the outcome of proteasome inhibition on endothelial senescence. Primary human umbilical vein endothelial cells (HUVECs) and primary mouse lung endothelial cells were employed in this study. In vitro replicative senescence was achieved by culturing HUVECs until they ceased to proliferate (15‐17 cumulative population doublings) and premature senescence was obtained by subjecting HUVECs to H2O2. The role of the proteasome in the development of senescence was tested by applying the proteasome inhibitors MG132 and bortezomib