Researcher receives $3.52 million grant to study epicardial fat in arteries of heart

It's no secret that a diet high in fat and sugar can lead to extra fat around the waistline. But it's what the diet will do to a specific type of fat around the heart that caught the attention of a group of Creighton researchers.

The National Institutes of Health (NIH) awarded Devendra K. Agrawal, Ph.D., professor of biomedical sciences, internal medicine and medical microbiology and immunology and senior associate dean for clinical and translational research at Creighton University School of Medicine, a five-year, $3.52 million grant to study epicardial fat and its role in the development and recurrence of atherosclerosis in the arteries of the heart. This narrowing and hardening of the arteries can result in coronary artery disease, the number one killer of Americans. Joining Agrawal on the study are Creighton faculty members Michael Del Core, M.D., William Hunter, M.D., and Subhash Paknikar, M.D.

"The need for answers is urgent," says Agrawal. "The incidence of both obesity and the insulin resistance resulting in type 2 diabetes - both of which are strong risk factors for inducing and accelerating inflammation in the vessels of the heart - is rising at an alarming rate in North America. In order to reduce heart diseases, enhance quality of life and improve longevity, we need to better understand the biology behind these processes and then identify new methods of treatment."

In this biologic battle-of-the-bulge, the four Creighton researchers have set their sights on epicardial fat, the fat tissue that covers approximately 80 percent of the heart's surface and is in especially close proximity to the coronary arteries. Healthy hearts use this fat as an energy source, but in the presence of a high-fat diet or in obese patients, the nature of the fat changes. Instead of fueling the heart, the epicardial fat releases mediators which can accelerate inflammation in the coronary arteries. This inflammation decreases dilation of the arteries and enhances the growth of cells that can ultimately block the flow of blood to and from the heart.

Agrawal believes this change may be involved in the initial development of atherosclerosis as well as the reason why some patients experience a re-narrowing of the artery even after a coronary intervention such as angioplasty or stenting.

"There is a great unmet need for new therapies for obese patients with heart disease who are undergoing invasive treatments such as angioplasty and bypass surgery," said Abby Ershow, Sc.D., nutrition program director at the NIH's National Heart, Lung, and Blood Institute (NHLBI). "These new therapies cannot be developed unless we understand the basic biological processes that affect how the patients will respond to treatments."

The grant will also fund research into how vitamin D deficiency may contribute to the problem and examine the effect of vitamin D supplementation on the re-narrowing of coronary arteries after balloon angioplasty and stenting.

"We have data to suggest that vitamin D deficiency can exacerbate the inflammatory characteristics of epicardial fat," said Agrawal. "By giving appropriate vitamin D supplementation, we believe we can restore healthy coronary activity and lessen the chances for future cardiovascular events following intervention."

Agrawal and his collaborators plan to use a swine model for the multi-disciplinary investigation. The cardiovascular system in this model is similar to humans, thus allowing the findings to translate well to the development of successful therapeutic approaches in human clinical trials.