Skeletal muscle Nox4 knockout prevents and Nox2 knockout blunts loss of maximal diaphragm force in mice with heart failure with reduced ejection fraction

Effects of aerobic exercise on cardiac function and gene expression of NADPH oxidases in diaphragm muscle of rats with aortic stenosis-induced heart failure

“…Skeletal muscle generates significant amounts of reactive oxygen species (ROS), which in physiological levels act as signaling molecules that modulate important biological processes. Exercise results in an acute increase in the production of ROS as evidenced by elevated biomarkers of oxidative damage in both blood and skeletal muscle ( Kumar et al, 2023 ). Zhao et al demonstrated the effects of exercise programs on the expression of both oxidative and antioxidant markers in skeletal muscle with different time points ( Zhao et al, 2013 ).…”

“…Zhao et al demonstrated the effects of exercise programs on the expression of both oxidative and antioxidant markers in skeletal muscle with different time points ( Zhao et al, 2013 ). These acute physiological changes during endurance exercise also plays an important role in cell signaling pathways involved in muscle adaptation to exercise ( Kumar et al, 2023 ). However, sustained high levels of ROS can cause oxidative damage to RNA, DNA, lipids, proteins, and cause cell death ( Gomes et al, 2017 ).…”

“…Although this study was limited to a transcriptional analysis of NADPH oxidases in the diaphragm muscle of rats with heart failure, previous and recent evidence have demonstrated the impact of this important source of oxidants in skeletal muscle contractile properties ( Ahn et al, 2015 ; Reyes et al, 2019 ; Powers et al, 2020 ). A recent study demonstrated that skeletal muscle specific knockout for Nox4 provided full protection against the loss of diaphragm maximal force, while the knockout of Nox2 provided partial protection in mice with heart failure ( Kumar et al, 2023 ).…”

Locomotor and respiratory muscle abnormalities in HFrEF and HFpEF

“…For example, reduction in mitochondrial ROS production by application of a mitochondrial-targeted antioxidant ( 136 ) or a neutral sphingomyelinase inhibitor ( 137 ) preserved diaphragm dysfunction in HF rats post MI. Interestingly, certain isoforms of Nox seem to play different roles in diaphragm abnormalities during development of HF with knock out of Nox2 restoring diaphragm function early and late after MI ( 138 , 139 ) whereas Nox4 knock out had no impact in on early diaphragm changes after acute MI ( 140 ) but restored function later on ( 139 ).…”