Vascular Biology & Immunopharmacology Group, Department of Pharmacology, Monash University, Victoria 3800, Australia.
Nat Rev Drug Discov. 2011 Jun;10(6):453-71. doi: 10.1038/nrd3403.
NADPH oxidases are a family of enzymes that generate reactive oxygen species (ROS). The NOX1 (NADPH oxidase 1) and NOX2 oxidases are the major sources of ROS in the artery wall in conditions such as hypertension, hypercholesterolaemia, diabetes and ageing, and so they are important contributors to the oxidative stress, endothelial dysfunction and vascular inflammation that underlies arterial remodelling and atherogenesis. In this Review, we advance the concept that compared to the use of conventional antioxidants, inhibiting NOX1 and NOX2 oxidases is a superior approach for combating oxidative stress. We briefly describe some common and emerging putative NADPH oxidase inhibitors. In addition, we highlight the crucial role of the NADPH oxidase regulatory subunit, p47phox, in the activity of vascular NOX1 and NOX2 oxidases, and suggest how a better understanding of its specific molecular interactions may enable the development of novel isoform-selective drugs to prevent or treat cardiovascular diseases.
NADPH 氧化酶是一类产生活性氧（ROS）的酶。在高血压、高胆固醇血症、糖尿病和衰老等情况下，NOX1（NADPH 氧化酶 1）和 NOX2 氧化酶是动脉壁中 ROS 的主要来源，因此它们是导致氧化应激、内皮功能障碍和血管炎症的重要因素，而这些正是动脉重塑和动脉粥样硬化的基础。在这篇综述中，我们提出了一个观点，即与使用传统抗氧化剂相比，抑制 NOX1 和 NOX2 氧化酶是对抗氧化应激的一种更优方法。我们简要描述了一些常见的和新兴的潜在 NADPH 氧化酶抑制剂。此外，我们强调了 NADPH 氧化酶调节亚基 p47phox 在血管 NOX1 和 NOX2 氧化酶活性中的关键作用，并提出了如何更好地理解其特定的分子相互作用，可能会促进开发新型同工酶选择性药物来预防或治疗心血管疾病。
