The regulation of cardiac intermediary metabolism by NADPH oxidases

NADPH oxidases (NOXs), enzymes whose primary function is to generate reactive oxygen species, are important regulators of the heart's physiological function and response to pathological insults. The role of NOX-driven redox signalling in pathophysiological myocardial remodelling, including proc...

Full description

Saved in:
Bibliographic Details
Published in:Cardiovascular research 2023-01, Vol.118 (17), p.3305-3319
Main Authors: Nabeebaccus, Adam A, Reumiller, Christina M, Shen, Jie, Zoccarato, Anna, Santos, Celio X C, Shah, Ajay M
Format: Article
Language:English
Subjects:
Heart
Myocardium - metabolism
NADPH Oxidase 4 - metabolism
NADPH Oxidases - metabolism
Oxidative Stress
Protein Isoforms - metabolism
Reactive Oxygen Species - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:NADPH oxidases (NOXs), enzymes whose primary function is to generate reactive oxygen species, are important regulators of the heart's physiological function and response to pathological insults. The role of NOX-driven redox signalling in pathophysiological myocardial remodelling, including processes such as interstitial fibrosis, contractile dysfunction, cellular hypertrophy, and cell survival, is well recognized. While the NOX2 isoform promotes many detrimental effects, the NOX4 isoform has attracted considerable attention as a driver of adaptive stress responses both during pathology and under physiological states such as exercise. Recent studies have begun to define some of the NOX4-modulated mechanisms that may underlie these adaptive responses. In particular, novel functions of NOX4 in driving cellular metabolic changes have emerged. Alterations in cellular metabolism are a recognized hallmark of the heart's response to physiological and pathological stresses. In this review, we highlight the emerging roles of NOX enzymes as important modulators of cellular intermediary metabolism in the heart, linking stress responses not only to myocardial energetics but also other functions. The novel interplay of NOX-modulated redox signalling pathways and intermediary metabolism in the heart is unravelling a new aspect of the fascinating biology of these enzymes which will inform a better understanding of how they drive adaptive responses. We also discuss the implications of these new findings for therapeutic approaches that target metabolism in cardiac disease.
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/cvac030