Jin, Zhen-Gen , PhD
Shear stress signaling in hyperglycemia-induced endothelial dysfunction
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Complications, Complications\Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes, Signal Transduction (Non-Insulin Action), Signal Transduction (Non-Insulin Action)\Phosphatases-Kinases, Signal Transduction (Non-Insulin Action)\Transgenic Models
Type of Grant: Basic Science
Project Start Date: July 1, 2012
Project End Date: June 30, 2015
Diabetes mellitus and its associated complications are a major health problem in the developed world. Diabetics are two to four-times more likely to have cardiovascular diseases than general population. Atherosclerosis is the leading cause of the morbidity and mortality in patients with diabetes mellitus. Clinically, while angioplasty therapies for atherosclerotic disease have been very successful in nondiabetic individuals, it shows limited success in diabetic patients. Thus, understanding the mechanisms of diabetic atherosclerosis is essential in order to ameliorate diabetic atherosclerotic disease. Normally atherosclerosis tends to occur at predisposed regions exposed to proatherogenic disturbed flow (d-flow), while steady laminar flow (s-flow) with high fluid shear stress at straight arteries is atheroprotective. Clinical studies show that atherosclerosis in diabetes mellitus is characterized by diffuse lesion formation, even occurring at s-flow areas of blood vessels. However, the cellular and molecular mechanisms for diabetic diffuse atherosclerosis remain unclear.
Our exciting preliminary data showed that hyperglycemia in diabetes impaired s-flow signaling in vascular endothelial cells, which could explain why diabetic atherosclerotic lesions also developed in the areas of s-flow that is supposed to be atheroprotective. Endothelial dysfunction in diabetes mellitus is a hallmark for the development of atherosclerosis. The proposed studies will examine the mechanisms by which hyperglycemia impaired s-flow signal transduction, leading to diabetic endothelial dysfunction and atherosclerosis. A better understanding of mechanisms for diabetic atherosclerosis could reveal novel therapeutic targets for the treatment of diabetic cardiovascular complications.
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 diabetes-associated vascular endothelial dysfunction. Endothelial dysfunction is a hallmark of atherosclerotic cardiovascular disease. However, the mechanisms by which diabetes induces endothelial dysfunction remain unknown. Our studies proposed in this project will provide new insight into signaling pathways leading to endothelial dysfunction in diabetic conditions, which may help us to develop new therapeutic strategies to prevent and treat diabetic cardiovascular complications.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Cardiovascular disease is a major complication and the leading cause of disability and premature death among people with diabetes. Our project is designed to understand how diabetes promotes cardiovascular disease. The results of this project may indicate that the strategies to maintain normal signaling from blood flow may prevent endothelial cell dysfunction and thus help with diabetic induced cardiovascular complications.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
With an increase in he prevalence of diabetes in the people consuming western diets and the concurrent mortality rates associated with cardiovascular disease, I feel that my research can help diabetic patients. This award will support my research on diabetes-associated vascular endothelial dysfunction and cardiovascular disease.
In what direction do you see the future of diabetes research going?
The future direction of diabetes research will involve improving quality and longevity of life for patients. Thus it is important to understand how high blood glucose levels (hyperglycemia) cause many problems with diabetes, in particular diabetes-associated cardiovascular complications which lead to a poorer quality of life and a high mortality among people suffering from diabetes.
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