“…The decreased protein level of SERCA2a and p16-phospholamban leads to left ventricular diastolic dysfunction and elevated arterial blood pressure [80]. Activation of SERCA can accelerate the reuptake of Ca 2+ by SR, which would improve the diastolic dysfunction of myocardium, and result in strong antiarrhythmic effect [81,82]. Our groups found that the S-glutathiolation of the amino acid residue Cys674 (C674) is key to the increase of the activity in SERCA2 under physiological conditions [83,84], but this post-translational protein modification is prevented by the irreversible oxidation of C674 thiol in pathology hallmarked by high level of ROS, including atherosclerosis, aortic aneurysms, aging and hypertension [83,[85][86][87].…”