Identification of Protein Disulfide Isomerase as a Cardiomyocyte Survival Factor in Ischemic Cardiomyopathy

Identification of Protein Disulfide Isomerase as a Cardiomyocyte Survival Factor in Ischemic Cardiomyopathy Anna Severino, Mara Campioni, Stefania Straino, Fadi N. Salloum, Nina Schmidt, Ulrike Herbrand, Stilla Frede, Gabriele Toietta, Giuliana Di Rocco, Rossana Bussani, Furio Silvestri, Maddalena Piro, Giovanna Liuzzo, Luigi M. Biasucci, Pasquale Mellone, Florinda Feroce, Maurizio Capogrossi, Feliciano Baldi, Joachim Fandrey, Michael Ehrmann, Filippo Crea, Antonio Abbate, Alfonso Baldi The Protein Disulfide Isomerase (PDI) gene is up-regulated in the viable peri-infarct myocardium of human hearts within the first days after infarction. This up-regulation is inversely correlated with cardiomyocyte apoptosis and with signs of remodeling. An in vitro model of cardiac hypoxia-ischemia confirms the up-regulation of PDI after hypoxic stress and its anti-apoptotic effects. These actions of PDI are mediated by cooperation with endoplasmic reticulum oxidoreductin 1 and by its modulation of the activity of zinc-superoxide dismutase. Finally, adenovirus-mediated PDI over-expression to the heart in a mouse model of myocardial infarction reduces cardiomyocyte apoptosis and prevents cardiac remodeling.