News & Research

    University of Louisville, Louisville, Kentucky

Role of HIF-1 in hypertrophyic heart of diabetics

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Integrated Physiology, Integrated Physiology\Muscle, Signal Transduction (Non-Insulin Action), Signal Transduction (Non-Insulin Action)\Transcriptional Regulation

Type of Grant: Basic Science

Project Start Date: January 1, 2012

Project End Date: December 31, 2014

Research Description

Heart growth in infant and or physiological hypertrophy observed in physical training is an adaptive process that is not associated with contractility impairments. To response to physiological hypertrophy, heart activates hypoxia-inducible factor-1alpha (HIF-1alpha) to produce more new blood vessel formation-related growth factors to provides oxygen and nutrients for increased demands in hypertrophic heart. However, diabetes damages this adaptive function. The aim of this project is to investigate whether HIF-1 is required for the adaptation to hypertrophy in diabetic heart, and to investigate the potential mechanisms. The results obtained from this project will have potential translational significance by providing potential therapeutic targets in preventing the progression of hypertrophy to failure in diabetic heart.

Research Profile

What area of Diabetes Research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

Heart growth in infant and/or physiological hypertrophy observed in physical training is an adaptive process that is not associated with contractility impairments. To response to physiological hypertrophy, heart activates a transcription factor-hypoxia-inducible factor-1alpha (HIF-1) to produce more new blood vessel formation-related growth factors to provides oxygen and nutrients for increased demands in hypertrophic heart. However, diabetes damages this adaptive function. The aim of this project is to investigate whether HIF-1 is required for the adaptation to hypertrophy in diabetic heart, and to investigate the potential mechanisms. The results obtained from this project will have potential translational significance by providing potential therapeutic targets in preventing the progression of hypertrophy to failure in diabetic heart.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Cardiovascular diseases have become one of the leading causes of increased morbidity and mortality in both type 1 and type 2 diabetes. A fundamental understanding of the basic mechanisms related to glucose and metabolic signaling in the heart is not yet clear. Heart failure is a final common consequence of various heart diseases and is a leading cause of mortality. Hypertrophy is initially an adaptive response to maintain normal cardiac contractile function by increasing ventricular wall thickness. However, this adaptive response is only a short-term solution. While conditions leading to heart injury have been well studied, the endogenous protective responses during hypertrophy are poorly understood, especially in diabetic patients. Our project is researching the mechanisms of why diabetes worsens the adaptive response of the hypertrophic heart and therefore causes heart failure. By understanding the nature of this adaptation process in diabetic heart, we will be able to design a better strategy and drug for preventing and curing this life-threatening diabetic complication.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

My career goal is to become an established research scientist in the area of diabetic cardiovascular complication, particularly diabetic cardiomyopathy and thereby contribute to the development of new treatment strategy to this disease. The aims of my research are: (1) to understand the mechanism of diabetic cardiovascular complications, (2) to develop effective strategies to prevent and ameliorate diabetic cardiomyopathy. Stemming from my background, I have a special interest in the basic research to explore the molecular mechanisms behind the diseases, particularly in the area of how tissue hypoxia and metal regulate the molecular pathway in diabetic heart. I believe that the combination of multidisciplinary effort is very important for finding a cure to this life-threatening disease.

Diabetes is spreading with a very fast pace worldwide. You can hear the bad news that somebody around you is newly diagnosed to be diabetic frequently. You can see that the patients are suffering the diabetic complications every day. To become involved in diabetes research is important for me because it is not only my personnel interest, but also fits my research experience and my career goal. Receiving this award will help me to continue my diabetic research and bridge me to obtain other funding such as NIH finding.

In what direction do you see the future of diabetes research going?

Although we have put a lot of efforts on diabetic research, it is still not clear for some fundamental mechanisms in diabetic etiology, prevention and therapy. Therefore, basic research is clearly very important. However, translational research should receive more investigative attention. This is because of the increasing demand not only in terms of economy and increasing number of patients, but also the close inter-correlation of basic research and translational research.