Search Results
Search for other papers by Tania Medali in
Google Scholar
PubMed
Search for other papers by Dominique Couchie in
Google Scholar
PubMed
Search for other papers by Nathalie Mougenot in
Google Scholar
PubMed
Search for other papers by Maria Mihoc in
Google Scholar
PubMed
Search for other papers by Olaf Bergmann in
Google Scholar
PubMed
Search for other papers by Wouter Derks in
Google Scholar
PubMed
Search for other papers by Celio X Santos in
Google Scholar
PubMed
Search for other papers by Bertrand Friguet in
Google Scholar
PubMed
Search for other papers by Mustapha Rouis in
Google Scholar
PubMed
Graphical abstract
Experimental Myocardial infarction (MI) using ligation procedure induces cardiac dysfunction, high level of ROS, inflammation, apoptosis, fibrosis and cardiomyocyte (CM) loss. AAV overexpressing human Trx-2, specifically in CM mitochondria improves mouse cardiac function, reduces the size of cardiac infarct, increases the expression of cardiac anti-inflammatory markers, reduces apoptosis and oxidative stress. However, it does not increase CM proliferation.
Abstract
Introduction and objective
Myocardial infarction (MI), which in general results from complications of atherosclerosis, is characterized by high inflammation and cardiomyocytes (CMs) apoptosis and by major loss of CMs. 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
The current study unveils the complexities of MI and highlights mitochondrial Trx-2 role. Post-MI, marked by inflammation, 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.
