Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets.

Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets.
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DOI:
10.1038/nrd3403
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发表时间:
2011-06
影响因子:
120.1
通讯作者:
Sobey, Christopher G.
Sobey, Christopher G.
中科院分区:
医学1区
文献类型:
--
作者:
Drummond, Grant R.;Selemidis, Stavros;Griendling, Kathy K.;Sobey, Christopher G.

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NADPH氧化酶是产生活性氧(ROS)的酶家族。NOX1(NADPH氧化酶1)和NOX2氧化酶是动脉壁中ROS的主要来源,如高血压、高胆固醇血症、糖尿病和衰老,因此它们是氧化应激、内皮功能障碍和血管炎症的重要贡献者,而这些是动脉重塑和动脉粥样硬化形成的基础。在这篇综述中,我们提出了这样一个概念,即与使用常规抗氧化剂相比,抑制NOX 1和NOX 2氧化酶是对抗氧化应激的上级方法。我们简要介绍了一些常见的和新兴的假定NADPH氧化酶抑制剂。此外,我们强调了NADPH氧化酶调节亚基p47 phox在血管NOX 1和NOX 2氧化酶活性中的关键作用,并建议如何更好地了解其特定的分子相互作用,从而能够开发新型亚型选择性药物来预防或治疗心血管疾病。
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.
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