Thomas Shane R, Witting Paul K, Drummond Grant R
Centre for Vascular Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Antioxid Redox Signal. 2008 Oct;10(10):1713-65. doi: 10.1089/ars.2008.2027.
The endothelium is essential for the maintenance of vascular homeostasis. Central to this role is the production of endothelium-derived nitric oxide (EDNO), synthesized by the endothelial isoform of nitric oxide synthase (eNOS). Endothelial dysfunction, manifested as impaired EDNO bioactivity, is an important early event in the development of various vascular diseases, including hypertension, diabetes, and atherosclerosis. The degree of impairment of EDNO bioactivity is a determinant of future vascular complications. Accordingly, growing interest exists in defining the pathologic mechanisms involved. Considerable evidence supports a causal role for the enhanced production of reactive oxygen species (ROS) by vascular cells. ROS directly inactivate EDNO, act as cell-signaling molecules, and promote protein dysfunction, events that contribute to the initiation and progression of endothelial dysfunction. Increasing data indicate that strategies designed to limit vascular ROS production can restore endothelial function in humans with vascular complications. The purpose of this review is to outline the various ways in which ROS can influence endothelial function and dysfunction, describe the redox mechanisms involved, and discuss approaches for preventing endothelial dysfunction that may highlight future therapeutic opportunities in the treatment of cardiovascular disease.
内皮细胞对于维持血管稳态至关重要。内皮型一氧化氮合酶（eNOS）合成的内皮源性一氧化氮（EDNO）的产生是这一作用的核心。内皮功能障碍表现为EDNO生物活性受损，是包括高血压、糖尿病和动脉粥样硬化在内的各种血管疾病发生发展过程中的一个重要早期事件。EDNO生物活性的受损程度是未来血管并发症的一个决定因素。因此，人们越来越关注确定其中涉及的病理机制。大量证据支持血管细胞产生活性氧（ROS）增加具有因果作用。ROS直接使EDNO失活，作为细胞信号分子发挥作用，并促进蛋白质功能障碍，这些事件促成了内皮功能障碍的发生和发展。越来越多的数据表明，旨在限制血管ROS产生的策略可以恢复患有血管并发症的人的内皮功能。本综述的目的是概述ROS影响内皮功能和功能障碍的各种方式，描述其中涉及的氧化还原机制，并讨论预防内皮功能障碍的方法，这些方法可能会突出心血管疾病治疗中的未来治疗机会。
