Dworakowski Rafał, Alom-Ruiz Sara P, Shah Ajay M
King's College London School of Medicine, The James Black Centre, Cardiovascular Division, London, UK.
Pharmacol Rep. 2008 Jan-Feb;60(1):21-8.
Endothelial dysfunction comprising impairment of endothelium-dependent vasodilator function and increased endothelial activation contributes to the pathophysiology of cardiovascular diseases such as atherosclerosis, diabetic vasculopathy, heart failure and hypertension. The changes in endothelial phenotype in these conditions occur in response to diverse stimuli including inflammatory cytokines, activation of renin-angiotensin-aldosterone system, hyperlipidaemia, hyperglycemia, ischemia-reperfusion and mechanical forces. An increased production of reactive oxygen species (ROS), such as superoxide and H(2)O(2) is involved in the genesis of these alterations in endothelial phenotype. The NADPH oxidases, Nox2 and Nox4, are major sources of ROS in endothelial cells and are implicated both in vasodilator dysfunction and in the modulation of redox-sensitive signalling pathways that influence endothelial cytoskeletal organisation, adhesion molecule expression, permeability, growth, migration and other functions. NADPH oxidases appear to be especially important in redox signalling in that they are specifically activated by diverse agonists and regulate the activation of downstream protein kinases, transcription factors and other biological molecules. This review provides an overview of NADPH oxidase structure and regulation in endothelial cells and their role in pathophysiology, focussing particularly on endothelial activation.
内皮功能障碍包括内皮依赖性血管舒张功能受损和内皮激活增加，这在动脉粥样硬化、糖尿病血管病变、心力衰竭和高血压等心血管疾病的病理生理学中起作用。在这些情况下，内皮表型的变化是对多种刺激的反应，这些刺激包括炎性细胞因子、肾素 - 血管紧张素 - 醛固酮系统激活、高脂血症、高血糖、缺血再灌注和机械力。活性氧（ROS）如超氧化物和H₂O₂的产生增加参与了内皮表型的这些改变的发生。NADPH氧化酶Nox2和Nox4是内皮细胞中ROS的主要来源，并且与血管舒张功能障碍以及影响内皮细胞骨架组织、黏附分子表达、通透性、生长、迁移和其他功能的氧化还原敏感信号通路的调节有关。NADPH氧化酶在氧化还原信号传导中似乎特别重要，因为它们被多种激动剂特异性激活并调节下游蛋白激酶、转录因子和其他生物分子的激活。本综述概述了内皮细胞中NADPH氧化酶的结构和调节及其在病理生理学中的作用，特别关注内皮激活。
