Grant: Operating Grant

Enlargement of the heart occurs when the heart is continuously exposed to conditions such as elevated blood pressure and/or increases in the amount of certain molecules, such as hormones, in the blood. Certain factors, including endothelin, also stimulate the heart to enlarge, or hypertrophy. We are investigating how endothelin, a naturally occurring regulatory protein, produces this enlargement of the heart. If the underlying cause for hypertrophy (e.g., increased endothelin release, high blood pressure) continue to be present and hypertrophy continues, a point is reached where the heart can no longer function properly. In this proposal, the means by which endothelin stimulates the muscle cells of the heart to enlarge are being studied. There are many steps in the chain of events initiated by endothelin acting upon a cardiac muscle cell. The first step is the interaction of endothelin with specialized proteins, dedicated to binding endothelin, called receptors. The final results include changes in the growth and function of the heart. The muscle cells of the heart contain two types of endothelin receptor. These receptors activate a network of signalling systems, similar to a telephone network, within the cell. In this project, the function of endothelin receptors that are located on the cell nucleus will be studied to determine their role in regulating the growth and function of muscle cells in the heart.