Mitochondrial DNA is a danger to the heart

• Main Author: Mariero, Lars Henrik
• Format: Dissertation
• Language: English

Myocardial infarction remains a major killer world-wide. The preservation of cardiac muscle cells is critical to patient outcomes after myocardial infarction. During myocardial infarction, cardiac muscle cells die and release cellular components that may cause inflammation and damage viable heart tissue. Mitochondrial DNA (mtDNA) is one of the potentially damaging components. The aim of this thesis was to improve understanding of the potentially harmful role of mtDNA in the setting of myocardial infarction. This was based on a patient study and a series of animal and cell experiments. We found that patients with myocardial infarction have elevated levels of mtDNA in their blood and that the heart is a likely source. mtDNA from patients induced an inflammatory reaction in cells and also triggered inflammation in mice. Further, we found that mtDNA induced cardiac cell death and impaired mitochondrial function. We also found that the protein nucleolin, which is expressed on the cell membrane of cardiomyocytes, could be a possible route for internalization of potentially damaging mtDNA and thus a potential treatment option.