Irani, Kaikobad , MD
SIRTUIN1-modulated development of Atrial Fibrillation in Diabetes
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Complications\ Macrovascular-Atherosclerotic CVD and Human Diabetes, Complications\Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes
Type of Grant: Basic Science
Project Start Date: January 1, 2013
Project End Date: December 31, 2015
Atrial fibrillation is a heart rhythm disturbance that can lead to stroke, heart failure, and death. Patients with diabetes are prone to developing atrial fibrillation. Atrial fibrillation can result from disturbances in the conduction of sodium (via sodium channels) in heart muscle cells. In this application we propose to test the hypothesis that sodium conduction in heart muscle cells is disturbed in diabetes, and aim to explore the role of a protein SIRTUIN1, which acts on sodium channels in the heart, in restoring normal sodium conduction.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and curing diabetes?
This work will seek to explore the molecular basis for a well-known association between diabetes and atrial fibrillation. Atrial fibrillation is the most common heart rhythm disturbance encountered in clinical practice. It increases the risk of stroke, heart failure, and death. Individuals with diabetes have increased lifetime risk of developing atrial fibrillation, but why diabetes leads to this heightened susceptibility is not known. This project will ask if diabetes makes the heart more susceptible to atrial fibrillation by decreasing the longevity protein SIRTUIN1 in the heart.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond??
Patients with diabetes have a two-fold higher risk of having atrial fibrillation during their lifetimes compared to individuals without diabetes, thus increasing their lifetime risk of developing complications from atrial fibrillation such as stroke, heart failure, and death. By understanding the molecular underpinnings of why the diabetic heart is more prone to atrial fibrillation, this project could identify targets to which drugs could be developed to reduce the risk of atrial fibrillation in patients with diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?
As a practicing cardiologist, I commonly, and increasingly, see patients with diabetes in my clinical practice. I see the many ways diabetes can damage the heart, leading to malfunction of the heart, including . This is what motivates me to understand how diabetes impacts the heart. This award will allow me to better understand how diabetes affects the normal electrical activity of heart muscle cells, and whether this effect is responsible for a very common heart rhythm disturbance.
In what direction do you see the future of diabetes research going?
Diabetes is a complex disease, and its cure will require complex solutions. Genetics plays a very important role in the development of diabetes, and is also likely to play an important part in therapies to combat the disease. Understanding how the genetic background increases, or decreases, susceptibility to development of diabetes will be the key to the design of new therapies.
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