Acute myocardial infarction (AMI) is characterized by the death of cardiomyocytes caused by prolonged ischemia. Patients with post-infarction remodeling have the highest risk of developing symptomatic heart failure, one of the most important causes of morbidity and mortality worldwide. Post-infarction remodeling promotes fibrotic repair of the cell's death area and, in the non-infarcted area, hypertrophic elongation of myocytes and interstitial fibrosis, resulting in an increase in wall mass and also in the chamber, with progressive decline in ventricular performance. Studies have shown that, in ischemic cardiomyopathies, the stress of endoplasmic reticulum (ER) can lead to the apoptosis of cardiac cells, facilitating the fibrotic remodeling and promoting the inflammatory response, which contributes for development and progression of cardiac insufficiency. This stress is associated with an accumulation of unfolded proteins, which can form toxic protein aggregates to the cells. To defend themselves, cells activate a response to unfolded proteins (UPR, from English, Unfolded Protein Response). Peroxiredoxin-4 (Prdx 4) participates in the oxidative processing of proteins in the ER and can represent one important component of this response. The aim of this study is to evaluate the effect of myocardial ischemia on the expression of PRDX4 and UPR-related genes in the presence or absence of diacerein, an anti-inflammatory agent with demonstrated action in the post-AMI treatment. We believe that this project can contribute to a better understanding of the mechanisms of ventricular remodeling, with emphasis on the role of the UPR and the diacerein in this process, with the possible identification of therapeutic targets.
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