Increase of NADPH oxidase 3 in heart failure of hereditary cardiomyopathy

Abstract

During the development of heart failure in humans and animal models, an increase in reactive oxygen species (ROS) levels was observed. However, there is no information whether this increase of ROS is associated with an increase in the density of specific isoforms of NADPH oxidases (NOXs) 1–5. The objective of this study was to verify whether the densities of NOXs 1–5 change during the development of heart failure. Using the well-known model of cardiomyopathic hamsters, the UM-X 7.1 line, a model that strongly resembles the pathology observed in humans from a morphological and functional point of view, our studies showed that, as in humans, NOXs 1–5 are present in both normal and UM-X7.1 hamster hearts. Even though the densities of NOXs 2 and 5 were unchanged, the levels of both NOXs 1 and 4 significantly decreased in UM-X7.1 hamster hearts during heart failure. These changes were accompanied with a significant increase in NOX3 level. These results suggest that, during heart failure, NOX3 plays a vital role in compensating the decrease of NOXs 1 and 4. This increase in NOX3 may also be responsible, at least in part, for the reported increase in ROS levels in heart failure.

On the Clinical Pharmacology of Reactive Oxygen Species

“…NOX3 appears to have the most restricted distribution, e.g., in the inner ear, where it is essential for the formation of otoconia, calcium carbonate crystals in the vestibule responsible for the detection of linear acceleration, gravity, and audition (Paffenholz et al, 2004;Kiss et al, 2006). A recent study, however, showed NOX3 overexpression in heart failure, suggesting new physiologic roles for this isoform (Bkaily et al, 2019). Conversely, NOX4 has the most ubiquitous distribution, including in the brain, endothelium, kidney, muscle, and adipose tissue.…”

NADPH Oxidase 3: Beyond the Inner Ear

“…The group mainly detected Nox4 mRNA expression, while Nox3 was only weakly expressed and accordingly focused on Nox4. Bkaily and colleagues further analyzed the role of Nox3 in this setting [1023]. For this purpose, they used the hereditary cardiomyopathy hamster model [1024][1025][1026], which is well established for cardiovascular disease studies [1027].…”

The Ryanodine Receptor as a Sensor for Intracellular Environments in Muscles

“…It was reported that inducible NOS expression increased in failing cardiomyocytes [ 127 ]. In addition to the increase in NOS, an increase in Nox expression has also been reported during heart failure [ 128 , 129 ]. Nox is an enzyme involved in the generation of ROS [ 130 , 131 ], and ROS promotes RyR oxidation and contributes to increased channel activity ( Figure 3 B).…”