Mitochondrial Transplantation as a New Therapeutic Approach Against Cardiac and Renal Consequences in Male Rats With...

Myocardial infarction (MI) is one of the leading causes of death worldwide. MI is associated with cardiac structural and functional alterations. Among these, cardiac fibrosis may be significantly influenced by mitochondrial dysfunction. We sought to evaluate whether the injection of functional mitochondria from healthy muscle could improve the detrimental consequences of MI.

Male Wistar rats were submitted to MI through the ligature of the left anterior descending coronary artery. Animals subjected to a sham operation (the same surgical procedure without fastening of the suture that passes through the LAD) were included as a reference group (Sham). At the time of surgery, either vehicle (PBS) or isolated mitochondria (equivalent to 180 μg of mitochondrial protein in 75 μL of vehicle) were directly injected into the myocardium around the ligation to half of the animals in each group. Animals were sacrificed 4 weeks after both MI induction and the evaluation of cardiac and systolic functions.

Cardiac mitochondrial transplantation was able to prevent the decrease in systolic function and the development of cardiac fibrosis in MI rats. These beneficial effects were accompanied by a reduction in cardiac hypertrophy, oxidative stress, endoplasmic reticulum stress activation, and inflammatory markers. We also evaluated the effects of mitochondrial transplantation by a proteomic analysis. In addition, cardiac mitochondrial transplantation was able to prevent the development of renal alterations observed in MI rats.

The data reveal novel mechanisms of mitochondrial transplantation effects and emerge as a novel therapeutic strategy under chronic diseases such as MI.