Vascular biology of superoxide-generating NADPH oxidase 5 (Nox5)- implications in hypertension and cardiovascular disease

Touyz, R. M. , Anagnostopoulou, A., Camargo, L. L., Rios, F. J. and Montezano, A. C. (2019) Vascular biology of superoxide-generating NADPH oxidase 5 (Nox5)- implications in hypertension and cardiovascular disease. Antioxidants and Redox Signaling, 30(7), pp. 1027-1040. (doi:10.1089/ars.2018.7583) (PMID:30334629) (PMCID:PMC6354601)

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Abstract

SIGNIFICANCE: NADPH oxidases (Nox) of which there are 7 isoforms (Nox1-5, Duox1/Duox2) are professional oxidases functioning as ROS-generating enzymes. ROS are signaling molecules important in physiological processes. Increased ROS production and altered redox signaling in the vascular system have been implicated in the pathophysiology of cardiovascular diseases, including hypertension, and have been attributed, in part, to increased Nox activity. RECENT ADVANCES: Nox1,2,4,5 are expressed and functionally active in human vascular cells. While Nox1,2,4 have been well characterized in models of cardiovascular disease, little is known about Nox5. This may relate to the lack of experimental models because rodents lack NOX5. However, recent studies have advanced the field by i) elucidating mechanisms of Nox5 regulation, ii) identifying Nox5 variants, iii) characterizing Nox5 expression and iv) discovery of Nox5 crystal structure. Moreover, studies in human Nox5-expressing mice have highlighted a putative role for Nox5 in cardiovascular disease. CRITICAL ISSUES: Although growing evidence indicates a role for Nox-derived ROS in cardiovascular (patho)physiology, the exact function of each isoform remains unclear. This is especially true for Nox5. FUTURE DIRECTIONS: Future directions should focus on clinically-relevant studies to discover the functional significance of Noxs, and Nox5 in particular, in human health and disease. Two important recent studies will impact future directions. Firstly, Nox5 is the first Nox to be crystalized. Secondly GWAS identified Nox5 as a novel blood pressure-associated gene. These discoveries, together with advancements in Nox5 biology and biochemistry, will facilitate discovery of drugs th at selectively target Noxs to interfere with uncontrolled ROS generation.

Item Type:Articles
Additional Information:The authors are also funded by the MRC (MC-PC-15076). RMT is supported through a BHF Chair Award (CH/12/29762).
Keywords:Clinical biochemistry, cell biology, biochemistry, physiology, molecular biology.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rios, Dr Francisco and Anagnostopoulou, Dr Aikaterini and Montezano, Dr Augusto and Touyz, Professor Rhian
Authors: Touyz, R. M., Anagnostopoulou, A., Camargo, L. L., Rios, F. J., and Montezano, A. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Antioxidants and Redox Signaling
Publisher:Mary Ann Liebert
ISSN:1523-0864
ISSN (Online):1557-7716
Published Online:18 October 2018
Copyright Holders:Copyright © 2018 Rhian M. Touyz, et al
First Published:First published in Antioxidants and Redox Signaling 30(7): 1027-1040
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607382Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)RG/13/7/30099RI CARDIOVASCULAR & MEDICAL SCIENCES
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES