The vascular endothelium is a critical interface, which separates the organs from the blood
and its contents. The endothelium has a wide variety of functions and maintenance of
endothelial homeostasis is a multi-dimensional active process, disruption of which has
potentially deleterious consequences if not reversed. Vascular injury predisposes to
endothelial apoptosis, dysfunction and development of atherosclerosis. Endothelial
dysfunction is an end-point, a central feature of which is increased ROS generation, a
reduction in endothelial nitric oxide synthase and increased nitric oxide consumption. A
dysfunctional endothelium is a common feature of diseases including rheumatoid arthritis,
systemic lupus erythematosus, diabetes mellitus and chronic renal impairment. The
endothelium is endowed with a variety of constitutive and inducible mechanisms that act to
minimise injury and facilitate repair. Endothelial cytoprotection can be enhanced by
exogenous factors such as vascular endothelial growth factor, prostacyclin and laminar
shear stress. Target genes include endothelial nitric oxide synthase, heme oxygenase-1,
A20 and anti-apoptotic members of the B cell lymphoma protein-2 family. In light of the
importance of endothelial function, and the link between its disruption and the risk of
atherothrombosis, interest has focused on therapeutic conditioning and reversal of
endothelial dysfunction. A detailed understanding of cytoprotective signalling pathways, their
regulation and target genes is now required to identify novel therapeutic targets. The
ultimate aim is to add vasculoprotection to current therapeutic strategies for systemic
inflammatory diseases, in an attempt to reduce vascular injury and prevent or retard
atherogenesis.