Grant: Operating Grant

It is well established that people with diabetes are more likely to suffer from heart failure and are three times more likely to die from it than the rest of the population. One of the reasons for this is that people with diabetes develop a specific form of heart disease called diabetic cardiomyopathy. In this condition, the heart does not beat as well because the ability of the heart cells to contract is impaired. Our recent studies suggest that increased activity of a specific signaling pathway, known as the RhoA-rho kinase pathway, plays a very important role in this condition, because when rats with type 1 diabetes are treated with drugs that block signaling through this pathway, the ability of their hearts to contract improves. We have found that this occurs after administration of a single dose of the drugs, both in isolated hearts and in intact animals. Preliminary evidence suggests that this pathway is also hyperactive in hearts from rats with type 2 diabetes as well, meaning that it is a common consequence of diabetes. In the proposed research, we will investigate why inhibition of this pathway leads to improvement of the ability of the diabetic heart to contract. We have identified some targets of the RhoA-rho kinase pathway in diabetic hearts and we will determine if they are responsible for the poor contraction of the heart. This research has the potential to lead to new information about the causes of diabetic cardiomyopathy, and to provide new strategies for its treatment.