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NADPH 氧化酶和氧化酶串扰在心血管疾病中的作用:新的治疗靶点。

NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets.

机构信息

Division of Molecular Medicine, Department of Anesthesiology, Division of Cardiology, Department of Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.

出版信息

Nat Rev Cardiol. 2020 Mar;17(3):170-194. doi: 10.1038/s41569-019-0260-8. Epub 2019 Oct 7.

Abstract

Reactive oxygen species (ROS)-dependent production of ROS underlies sustained oxidative stress, which has been implicated in the pathogenesis of cardiovascular diseases such as hypertension, aortic aneurysm, hypercholesterolaemia, atherosclerosis, diabetic vascular complications, cardiac ischaemia-reperfusion injury, myocardial infarction, heart failure and cardiac arrhythmias. Interactions between different oxidases or oxidase systems have been intensively investigated for their roles in inducing sustained oxidative stress. In this Review, we discuss the latest data on the pathobiology of each oxidase component, the complex crosstalk between different oxidase components and the consequences of this crosstalk in mediating cardiovascular disease processes, focusing on the central role of particular NADPH oxidase (NOX) isoforms that are activated in specific cardiovascular diseases. An improved understanding of these mechanisms might facilitate the development of novel therapeutic agents targeting these oxidase systems and their interactions, which could be effective in the prevention and treatment of cardiovascular disorders.

摘要

活性氧(ROS)依赖性 ROS 的产生是持续性氧化应激的基础,持续性氧化应激与高血压、主动脉瘤、高胆固醇血症、动脉粥样硬化、糖尿病血管并发症、心肌缺血再灌注损伤、心肌梗死、心力衰竭和心律失常等心血管疾病的发病机制有关。不同氧化酶或氧化酶系统之间的相互作用已被深入研究,以探讨其在诱导持续性氧化应激中的作用。在这篇综述中,我们讨论了每种氧化酶成分的病理生物学的最新数据,不同氧化酶成分之间的复杂串扰,以及这种串扰在介导心血管疾病过程中的后果,重点介绍了在特定心血管疾病中被激活的特定 NADPH 氧化酶(NOX)同工型的核心作用。对这些机制的深入了解可能有助于开发针对这些氧化酶系统及其相互作用的新型治疗药物,这可能对心血管疾病的预防和治疗有效。

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