Thioredoxin-2 protects mice against experimental myocardial infarction

Abstract

Introduction and objective: Myocardial infarction (MI), which in general results from complications of atherosclerosis, is characterized by high inflammation and CMs apoptosis and by major loss of cardiomyocytes. Regeneration of these lost CMs represents a major challenge for MI therapy. The increase of mitochondrial reactive oxygen species (ROS) is involved in cell cycle arrest which can be restarted by hypoxia or in the presence of ROS scavengers. Among ROS scavengers, mitochondrial Thioredoxin-2 (Trx-2), an important antioxidant protein, could play a role in the CMs renewal. Method: In this study, we investigated the effect of Trx-2 on mouse heart after an experimental MI. Results: Trx-2 improves mouse cardiac function, reduces cardiac infarction size and increases the expression of cardiac anti-inflammatory markers. In addition, it reduces apoptosis and oxidative stress in heart tissue of mice after MI but it does not increase CM proliferation in cell culture or in heart tissue. Conclusion: Mitochondrial Trx-2 effectively protects against heart infarction, likely via the reduction of oxidative stress, inflammation and apoptosis but not through CM renewal. Significance statement: This research unveils the complexities of myocardial infarction (MI) and highlights mitochondrial Thioredoxin-2's (Trx-2) role. Post-MI, marked by inflammation, cardiomyocyte (CM) apoptosis, and significant CM loss. Trx-2 emerges as a vital protector. Its intervention improves mouse cardiac function, reduces infarction size, and fosters an anti-inflammatory environment. By uncovering these mechanisms, the study suggests potential therapeutic strategies for oxidative stress, inflammation, and apoptosis in MI, positioning Trx-2 as a promising candidate for future cardiac interventions.