Grant: Operating Grant

When the health of the circulatory system is compromised by high blood pressure, the heart must work harder to maintain adequate blood flow through the brain, kidney and other critical organs. After prolonged periods of high blood pressure or in diseases such as diabetes, the heart becomes more stiff and pumping efficiency is reduced. The heart enlarges to compensate for the increased work that it must perform. This adaptive process of cardiac hypertrophy is an important step leading to heart failure, one of the most serious cardiovascular diseases that leads ultimately to death. Cardiac hypertrophy is an important process that precedes cardiac failure and is characterized by the conversion of cells that are normally found in the heart into specialized cells (myofibroblasts) that produce the protein collagen. The production and secretion of collagen by myofibroblasts makes the heart stiffer and a much less efficient pump. Currently, little is known about how forces acting on the heart cause fibroblasts to convert into myofibroblasts and activate these cells to produce collagens that stiffen the heart muscle. The purpose of this application is to investigate how the cells inside the heart muscle detect and respond to increased applied forces associated with cardiac overload. We are interested in determining how these forces affect the metabolism of the heart and convert cardiac fibroblasts into myofibroblasts. We hope to identify a signaling system in cardiac fibroblasts that is activated by force and that when blocked by chemical inhibitors of the signaling system, may prevent fibroblasts from converting to myofibroblasts, producing excessive collagen and interfering with heart function.