Acute myocardial infarction (AMI) leads to activation of unfolded protein response (UPR) following endoplasmic reticulum (ER) stress. Failing in the restoration of the proper folding activity in the ER can lead to apoptosis and cell death. While it can be easy to detect transcripts and proteins expression alterations during a pathological state, it can be difficult to address the importance of changes in protein expression in the physiopathological context. We found protein disulfide isomerase (PDI) increased expression in human autoptic heart samples correlating with cell survival following AMI. PDI enzymatic activity resulted to be important to achieve cardiomyocyte protection from hypoxic stress, dependent on its ability to relieve ER stress preventing accumulation of nonfolded proteins in the ER, and to enhance superoxide dismutase 1 (SOD-1) activity. Furthermore, adenoviral-mediated PDI overexpression in an in vivo mouse model of AMI prevented adverse cardiac remodeling reducing cardiomyocyte apoptosis. Finally, we suggest a method to detect alterations in normal redox state in PDI (and eventually in the PDI family's proteins) during pathologies in which ER stress is induced. Diabetes pathology correlates with increased risk of AMI and worse cardiac remodeling. We found an alteration in PDI redox state in the diabetic heart and suggest using this system for the detection of the redox state alteration to screen for therapies able to restore the proper redox state.
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