Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
- PMID: 21629295
- PMCID: PMC3361719
- DOI: 10.1038/nrd3403
Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
Abstract
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.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3361719/bin/nihms377394f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3361719/bin/nihms377394f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3361719/bin/nihms377394f3.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3361719/bin/nihms377394f4.gif)
Similar articles
-
Endothelial NADPH oxidases: which NOX to target in vascular disease?Trends Endocrinol Metab. 2014 Sep;25(9):452-63. doi: 10.1016/j.tem.2014.06.012. Epub 2014 Jul 23. Trends Endocrinol Metab. 2014. PMID: 25066192 Review.
-
Role of Nox isoforms in angiotensin II-induced oxidative stress and endothelial dysfunction in brain.J Appl Physiol (1985). 2012 Jul;113(2):184-91. doi: 10.1152/japplphysiol.00455.2012. Epub 2012 May 24. J Appl Physiol (1985). 2012. PMID: 22628375 Free PMC article.
-
Targeting NADPH oxidases in vascular pharmacology.Vascul Pharmacol. 2012 May-Jun;56(5-6):216-31. doi: 10.1016/j.vph.2012.02.012. Epub 2012 Mar 3. Vascul Pharmacol. 2012. PMID: 22405985 Free PMC article. Review.
-
Oxidative stress and endothelial dysfunction in aortas of aged spontaneously hypertensive rats by NOX1/2 is reversed by NADPH oxidase inhibition.Hypertension. 2010 Sep;56(3):490-7. doi: 10.1161/HYPERTENSIONAHA.109.149187. Epub 2010 Jul 6. Hypertension. 2010. PMID: 20606112
-
Neurotoxic activation of microglia is promoted by a nox1-dependent NADPH oxidase.J Neurosci. 2008 Nov 12;28(46):12039-51. doi: 10.1523/JNEUROSCI.3568-08.2008. J Neurosci. 2008. PMID: 19005069 Free PMC article.
Cited by
-
Structural basis of human NOX5 activation.Nat Commun. 2024 May 11;15(1):3994. doi: 10.1038/s41467-024-48467-y. Nat Commun. 2024. PMID: 38734761 Free PMC article.
-
Inositol Hexaphosphate as an Inhibitor and Potential Regulator of p47phox Membrane Anchoring.Biochemistry. 2024 May 7;63(9):1097-1106. doi: 10.1021/acs.biochem.4c00117. Epub 2024 Apr 26. Biochemistry. 2024. PMID: 38669178 Free PMC article.
-
Gene Expression and Prognostic Value of NADPH Oxidase Enzymes in Breast Cancer.Int J Mol Sci. 2024 Mar 19;25(6):3464. doi: 10.3390/ijms25063464. Int J Mol Sci. 2024. PMID: 38542437 Free PMC article.
-
Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba.Acta Pharm Sin B. 2024 Jan;14(1):1-19. doi: 10.1016/j.apsb.2023.09.014. Epub 2023 Sep 23. Acta Pharm Sin B. 2024. PMID: 38239238 Free PMC article. Review.
-
Oxidative stress in acute pulmonary embolism: emerging roles and therapeutic implications.Thromb J. 2024 Jan 12;22(1):9. doi: 10.1186/s12959-023-00577-1. Thromb J. 2024. PMID: 38216919 Free PMC article. Review.
References
-
- Dinauer MC. Disorders of neutrophil function: an overview. Methods Mol. Biol. 2007;412:489–504. - PubMed
-
- Santos CX, Tanaka LY, Wosniak J, Laurindo FR. Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase. Antioxid. Redox Signal. 2009;11:2409–2427. - PubMed
-
- Morris CD, Carson S. Routine vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the U. S. Preventive Services Task Force. Ann. Intern. Med. 2003;139:56–70. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous