Arkansas Researcher to Receive $1.3 Million NIH Grant to Study Vascular Complications of Diabetes

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Mahendra Kavdia, University of Arkansas

FAYETTEVILLE, Ark. – A biomedical engineering researcher at the University of Arkansas will receive a $1.3 million grant from the National Institutes of Health to study the causes of endothelial cell dysfunction, which significantly contributes to many diabetes-related vascular complications and cardiovascular disorders. The research will help medical researchers better understand the molecular mechanisms for endothelial cell dysfunction and will guide the development of new therapies for diabetes-related vascular problems.

“Scientists know that endothelial cell dysfunction is a common pathogenic framework of many vascular complications,” said Mahendra Kavdia, an assistant professor in the College of Engineering. “For example, we know that oxidative stress is a key event in endothelial cell dysfunction. But the underlying molecular mechanisms of this process remain poorly understood. Our investigation will improve this understanding.”

Endothelium is a single layer of thin cells that line blood vessels. In this case, the focus is on the function of endothelial cells for regulation of blood flow. Scientists have determined that in diabetes patients these cells do not function properly or fail, which results in a reduced availability of endothelial-cell-released nitric oxide, a key signaling molecule for the regulation of blood flow. So far, this is the primary marker for endothelial cell dysfunction.

Kavdia’s research team hypothesizes that this biochemical chain of events includes interaction between nitric oxide and reactive oxygen species that are influenced by many factors such as enzymes and antioxidants, and the release of nitric oxide and superoxide. To test this hypothesis, the researchers have been developing computational models to predict levels of nitric oxide, superoxide and peroxynitrite, a toxic biochemical produced by the interaction between nitric oxide and superoxide. With the aid of endothelial cells from human umbilical cords, the research team also has performed in vitro experiments to expose endothelial cells with oxidative stress. The grant from the National Heart, Lung and Blood Institute will allow the researchers to continue this integrated computational and experimental approach.

Specifically, researchers will determine the release of nitric oxide and superoxide from endothelial cells and the nature of cell damage in hyperglycemic conditions. They will also develop computational biotransport models to simulate experiments and predict levels of nitric oxide, superoxide and peroxynitrite. Finally, Kavdia’s team will develop multiscale computational models to explain underlying processes of oxidative stress in the microcirculation.

The grant will also help to significantly augment biomedical engineering research opportunities at the university.

Kavdia, the first biomedical engineering faculty member hired by the university, also has research projects supported by the American Heart Association. He recently received the Arthur C. Guyton Award for Excellence in Integrative Physiology and Medicine.

For background or more information about Kavdia’s research, please visit http://comp.uark.edu/~mkavdia/.