Mason Justin C
Vascular Science, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK.
Vascul Pharmacol. 2016 Nov;86:41-52. doi: 10.1016/j.vph.2016.08.002. Epub 2016 Aug 9.
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.
血管内皮是一个关键界面，它将器官与血液及其成分分隔开来。内皮具有多种功能，维持内皮稳态是一个多维度的活跃过程，如果不逆转，其破坏可能会产生有害后果。血管损伤易导致内皮细胞凋亡、功能障碍和动脉粥样硬化的发展。内皮功能障碍是一个终点，其核心特征是活性氧生成增加、内皮型一氧化氮合酶减少和一氧化氮消耗增加。功能失调的内皮是包括类风湿性关节炎、系统性红斑狼疮、糖尿病和慢性肾功能损害等疾病的共同特征。内皮具有多种组成性和诱导性机制，这些机制可将损伤降至最低并促进修复。血管内皮生长因子、前列环素和层流切应力等外源性因素可增强内皮细胞保护作用。靶基因包括内皮型一氧化氮合酶、血红素加氧酶-1、A20和B细胞淋巴瘤蛋白-2家族的抗凋亡成员。鉴于内皮功能的重要性及其破坏与动脉粥样硬化血栓形成风险之间的联系，人们的兴趣集中在内皮功能障碍的治疗性调节和逆转上。现在需要详细了解细胞保护信号通路、它们的调节和靶基因，以确定新的治疗靶点。最终目标是在当前系统性炎症性疾病的治疗策略中增加血管保护作用，以减少血管损伤并预防或延缓动脉粥样硬化的发生。
