Grant: Project Grant

1 in 12 Canadian adults currently live with heart disease, which as it progresses can lead to a heart attack and sudden death. Patients that survive this event are left with a damaged heart that over time will scar and gradually fail, with a heart transplant being one of the only treatment options. The immune system is regarded as a key regulator of the inflammatory and repair mechanisms in injured heart, thus targeting specific aspects of this response could help to guide how the heart heals. Our group has recently shown that the cavity (pericardium) that surrounds the heart is a source of protective immune cells. We hypothesize that these pericardial cells prevent scarring by communicating with cells in the heart, fibroblasts, that control the scarring process. We will study the communication between pericardial immune cells and fibroblasts of the heart following a heart attack. Combining a specialized tagging system for pericardial immune cells with high powered microscopes, we will track how these cells can travel from the pericardial space into the heart and visualize the nature and location of interactions with other cells such as fibroblasts. We will identify the specific molecules made by pericardial cells in these locations. To test how pericardial immune cells affect the fibroblast activation leading to scarring in the injured heart we will use two approaches: 1)Deplete or block pericardial immune cells from getting to the heart 2) Prevent the production of specific molecules by pericardial immune cells that regulate fibroblast activity. By understanding the locations and molecules that are important for the protective actions of pericardial immune cells, we aim to design targeted strategies to better optimize the healing process in the heart that will save lives and maintain quality of life for many Canadians.