When cardiomyocytes are subjected to mechanical distortion by physiological stretch, they activate NOX2 in the sarcoplasmic and t-tubular membranes, induce ROS production through a microtubule-dependent network (X-ROS signaling), activate oxidative stress, sensitize ryanodine receptors (RyRs) around the sarcoplasmic reticulum (SR), induce massive cytoplasmic calcium ion (Ca2 +) release and increase the incidence of arrhythmias and cardiomyopathy (48). This evidence concerns the gene CYBB and cardiomyopathy.