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

Patients with heart failure with reduced ejection fraction (HFrEF) experience diaphragm weakness that contributes to the primary disease symptoms of fatigue, dyspnea, and exercise intolerance. Weakness in the diaphragm is related to excessive production of reactive oxygen species (ROS), but the exact source of ROS remains unknown. NAD(P)H Oxidases (Nox), particularly the Nox2 and 4 isoforms, are important sources of ROS within skeletal muscle that contribute to optimal cell function.

Skeletal myopathy in a rat model of postmenopausal heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of all patients with heart failure and frequently affects postmenopausal women. The HFpEF condition is phenotype-specific, with skeletal myopathy that is crucial for disease development and progression. However, most of the current preclinical models of HFpEF have not addressed the postmenopausal phenotype.