Deletion of complement component 3 gene may protect the heart against ischemia-reperfusion injury

Acute myocardial infarction results in necrosis and initiation of a local sterile inflammation activated through Damage-Associated Molecular Patterns (DAMPs). Cells of the immune system are the most prominent cells dealing with pathogens, but non-immune cells can also respond to pathogens in a local manner, whereas production of pro-inflammatory cytokines activates a systemic inflammation and recruits immune cells to the site of tissue injury. Paradoxically, this immune response may cause further damage of surrounding healthy cells. The complement system is involved in innate immune responses protecting the host against invading pathogens. Activation of the complement system is managed through cleavage of the complement component 3 (C3). Previous findings suggest that blocking C3 reduce cell death after myocardial infarction. It has been proposed that activation of C3 can occur intracellularly in immune-competent cells, whether this is true for cardiac cells is still not known. We want to investigate the role of C3 in cardiac cells, and investigate if deletion of C3 is beneficial for myocardial necrosis in ischemia-reperfusion injury. This project can potentially lead to development of new anti-inflammatory therapeutic drugs for patients suffering from acute myocardial ischemia.