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.
Key points
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Activation of NADPH oxidase (NOX) has a critical role in the pathogenesis of cardiovascular diseases.
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Activation of NOX induces activation of downstream secondary oxidase systems, including uncoupled endothelial nitric oxide synthase, dysfunctional mitochondria and xanthine oxidase.
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Crosstalk between oxidases or oxidase systems sustains oxidative stress to mediate the development of cardiovascular diseases.
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Targeting NOXs as well as interactions between NOXs and secondary oxidase systems might be a novel therapeutic strategy for the prevention and treatment of cardiovascular diseases.
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Acknowledgements
The authors are supported by an AHA Postdoctoral Fellowship Award #14POST20380996 (Y.Z.), NIH National Heart, Lung, and Blood Institute (NHLBI) grants HL077440, HL088975 and HL119968, and an AHA Established Investigator Award 12EIA8990025 (H.C.).
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Zhang, Y., Murugesan, P., Huang, K. et al. NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets. Nat Rev Cardiol 17, 170–194 (2020). https://doi.org/10.1038/s41569-019-0260-8
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DOI: https://doi.org/10.1038/s41569-019-0260-8
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