Cardiac fibrosis and fibroblast phenotypes in heart failure: probing heterogeneity and pathways for reversibility

The heart is the muscular pump that ensures blood flow through the body. When the heart is damaged, this pump function fails, a condition known as heart failure. The most common cause of heart failure is the death and loss of muscle cells during a heart attack. The muscle cells are replaced by scar tissue that is made by another cell type, the fibroblasts. Fibroblasts are normally present in the heart and provide the necessary support structure for the muscle cells by weaving a fine fibrous matrix. After a heart attack, these fibroblasts will be ‘activated’ and transform into myofibroblasts to make a more dense matrix, rich in collagen. This is necessary for making scar tissue, but this also happens between the remaining healthy cells. With more collagen matrix between the heart cells, the heart become stiffer and this reduces the pump function. A similar process can also occur in other cardiac diseases, e.g. when the heart has to cope with high blood pressure.

In this project, we will study the properties of these activated myofibroblasts, by isolating them from small heart tissue samples obtained at the time of heart transplantation. We will more precisely define the processes that lead to activation and see if these processes are reversible. We  further examine whether we can ensure that scar is protected when we reduce the overactive myofibroblasts in the healthy heart tissue.