Grant: Project Grant

Each and every heartbeat is initiated by a natural pacemaker in our hearts called the sinoatrial node. Normal sinus node function leads to proper activation of the atria (the upper chambers of the heart). This sequence of events ensures our heart rate is normal and that the heart is properly able to pump blood to our bodies. Common forms of cardiovascular disease, including hypertension (high blood pressure) and heart failure result in serious damage to the sinoatrial node and the atria leading to arrhythmias (irregular, abnormal patterns in the heartbeat) such as sinoatrial node dysfunction and atrial fibrillation. Although sinoatrial node dysfunction and atrial fibrillation are very common in hypertension very little is known about why this happens our how they can be treated. Currently, people with sinoatrial node disease have to get an artificial pacemaker, which is costly and has a number of serious limitations. Similarly, current atrial fibrillation treatments are often not effective. My laboratory is one of only a few worldwide with the expertise to study the sinoatrial node (and the atria) in mice, including at the cellular and molecular level. This is critical because it enables us to make use of genetically altered mice in our experiments. We have discovered that a family of protective hormones, called natriuretic peptides, can protect against sinoatrial node disease and atrial fibrillation in mouse models of hypertension. Natriuretic peptide effects are complex because there are several forms of these hormones and they can cause their effects in a number of different ways. Our proposed experiments will help us understand the complex effects of natriuretic peptides in the diseased heart. Our ultimate goal is to use this information to generate new synthetic natriuretic peptides that are designed to enhance the beneficial effects of these hormones for the treatment and prevention of sinoatrial node disease and atrial fibrillation.