Epstein, Paul N.
Mitochondrial DNA damage in diabetic cardiomyopathy
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Complications\Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes
Type of Grant: Basic Science
Project Start Date: July 1, 2011
Project End Date: June 30, 2014
Diabetic cardiomyopathy is a prominent cause of heart failure in diabetic patients. Diabetic cardiomyopathy and other complications of diabetes develop over many years. It is still unknown what the mechanism is for this very slow but progressive damage to the heart and other organs in diabetes. The hypothesis to be tested in this proposal is that the prolonged time course of diabetic complications stems from gradual accumulation of damage to DNA present in the cellular energy creating structure, mitochondria. Mitochondria create high levels of the DNA damaging molecules called reactive oxygen species. To test this hypothesis Type 1 and Type 2 mouse models of diabetes will be bred to mice that have been created to provide protection of mitochondrial DNA in the heart. If the hypothesis is correct than diabetic cardiomyopathy will be significantly reduced and structure and function of cardiac mitochondria will be protected from diabetes in mice with reduced DNA damage. These studies will provide an understanding of the long term progression of cardiomyopathy in diabetic patients and a mechanism that can underlie other diabetic complications. If correct than DNA of mitochondria will be a new therapeutic target in diabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project focuses on diabetic cardiomyopathy and the role of mitochondrial DNA damage. Diabetic cardiomyopathy is a prominent cause of heart failure in diabetic patients. It is still unknown what the mechanism is for this very slow but progressive damage to the heart and other organs in diabetes. The hypothesis to be tested in this proposal is that the prolonged time course of diabetic complications stems from gradual accumulation of damage to DNA present in the cellular energy creating structure, mitochondria. If the hypothesis is correct than diabetic cardiomyopathy will be significantly reduced by protection of mitochondrial DNA. Proof of this will indicate that DNA of mitochondria is a new therapeutic target in diabetes for treatment of diabetic cardiomyopathy and other complications of diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
The results of this project may indicate that drugs and compounds can be developed that will prevent or slow the development of diabetic cardiomyopathy by reducing damage to mitochondrial DNA. Some antioxidant drugs may be effective. Successful results could also mean that other complications such as those that develop in the kidney and eye may also be benefited by the same drugs.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
My greatest ambition is to play a significant role in the improvement of patient life. My research efforts are motivated by a desire to help diabetic patients. This award will allow me to continue my work testing whether the prolonged and progressive worsening of complications in people with diabetes can be explained by the gradual accumulation of mitochondrial DNA damage. If this is correct than drugs should be tested for their ability to protect mitochondrial DNA.
In what direction do you see the future of diabetes research going?
Screening of drugs for prevention of diabetic complications needs to be speeded up. To do this we need biochemical, cellular and rodent models that reproduce the pathology of diabetic complications seen in patients.
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