Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Curr Vasc Pharmacol. 2012 Jan;10(1):77-93. doi: 10.2174/157016112798829751.
Persistent oxidative stress in the vascular wall may lead to endothelial dysfunction, a pathological process widely implicated in the morbidities observed in a spectrum of cardiovascular disease. The production of reactive oxygen species (ROS) is regulated by various oxidase enzymes and mitochondrial electron transport mechanisms. Nitric oxide (NO) is a key mediator of endothelial function via its effect on endothelium dependent vascular relaxation. Therapeutic interventions aimed to increase NO bioavailability in the vasculature may improve the long term cardiovascular outcome for healthy individuals, high-risk subjects, and patients with advanced atherosclerosis. Current therapeutic strategies focus on enhancing synthesis or lowering oxidative inactivation of NO in human vasculature. Of the available therapeutic agents, angiotensin converting enzyme inhibitors and statins have shown most promise at improving endothelial function and cardiovascular outcome after long term administration. Other therapeutic approaches may also be useful towards improving endothelial dysfunction. These strategies include targeting NO synthesis by modulation of endothelial nitric oxide synthase (eNOS) coupling, such as folates and tetrahydrobiopterin. Evidence for the benefits of gene therapy to improve endothelial function is also emerging. However, the long term direct clinical benefit of these strategies aimed to improve endothelial function still remains unclear.
血管壁中持续的氧化应激可能导致内皮功能障碍，这是一种广泛存在于多种心血管疾病中观察到的病态过程。活性氧（ROS）的产生受各种氧化酶和线粒体电子传递机制的调节。一氧化氮（NO）通过其对内皮依赖性血管舒张的影响，是内皮功能的关键调节剂。旨在增加血管中 NO 生物利用度的治疗干预措施可能会改善健康个体、高风险人群和晚期动脉粥样硬化患者的长期心血管结局。目前的治疗策略侧重于增强人类血管中 NO 的合成或降低其氧化失活。在现有治疗药物中，血管紧张素转换酶抑制剂和他汀类药物在长期给药后改善内皮功能和心血管结局方面显示出最大的潜力。其他治疗方法也可能有助于改善内皮功能障碍。这些策略包括通过调节内皮一氧化氮合酶（eNOS）偶联来靶向 NO 合成，例如叶酸和四氢生物蝶呤。改善内皮功能的基因治疗的益处的证据也在不断出现。然而，这些旨在改善内皮功能的策略的长期直接临床益处仍不清楚。
