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.
Keywords: Cytoprotection; Endothelial dysfunction; Endothelium; Shear stress; Vascular injury.
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