BOSTONHeart disease has been the number one killer in the U.S. for several decades. Diabetes is now the seventh most common cause of death here. Obesity is a risk factor for both conditions and estimates now show that nearly 70 percent of obese, type-2 diabetics will die of cardiovascular disease.
While this much is known, exactly how obesity and diabetes affect the heart still remains largely a mystery. Johnathan D. Tune, Ph.D., associate professor in the Department of Cellular and Integrative Physiology at Indiana University School of Medicine, is working to find an explanation for these connections. His work, examining these conditions in living pigs, isolated blood vessels, and cells alike, is revealing targets that could eventually be used to treat heart disease or slow its progression, perhaps eventually knocking it from the top cause of death.
For this novel research, the American Physiological Society has recognized the importance of Dr. Tune's work by awarding him the Henry Pickering Bowditch Lecture Award. The award is one of the highest offered by the society and is given to scientists younger than 42 years of age whose accomplishments are original and outstanding.
When Pigs Run:
As a Ph.D. student at the University of North Texas Health Science Center in Forth Worth, Dr. Tune's research focused on how to protect the heart from ischemic damagethe injury that takes place when the heart's cells are deprived of oxygen and results in a heart attack. He and his colleagues found that forcing the heart to use glucose as a primary fuel was able to protect the heart against this damage. Later, when he was a postdoctoral fellow at the University of Washington School of Medicine, he studied how the heart regulates blood flowsignals that it needs more or less oxygen.
Now, at Indiana University School of Medicine, Dr. Tune combines these interests to study how obesity and diabetes affect blood flow to the heart. He and his colleagues are examining this question in a variety of different ways. For example, one of their most useful models is obese pigs. The researchers surgically implant catheters and transducers in these animals so that coronary blood flow, blood pressure, and cardiac function can be continuously monitored while the animals are conscious and active. Part of their work involves exercising the animals, since exercise can trigger heart attacks in people.
"I always tell people that pigs don't fly, but ours do run on a treadmill," he says. "Just as physicians perform treadmill stress tests in patients suspected of having coronary disease, we use treadmill exercise to physiologically increase the workload of the heart in real time."
Dr. Tune and his colleagues also examine isolated blood vessels and smooth muscle cells in their pig model. These examinations have turned up a number of findings, including that obesity significantly decreases the function of specific potassium channels that are critical for the regulation of blood flow to the heart. Without enough of these channels, the heart may not receive enough blood and oxygen over time, which could lead to long-term damage.
Additional studies in Dr. Tune's laboratory are focused on the potential role of factors released from fat cells, including fat cells that normally surround the major coronary arteries. His recent work has shown that one of these factors, a chemical called leptin, can impair the function of cells that line blood vessels, potentially contributing to the development of coronary artery disease.
From Pigs to People:
Though much of his research takes place in pigs, his ultimate goal is to find pharmaceutical targets for treating heart disease in people. "By understanding how obesity and diabetes leads to the development of cardiovascular disease we hope to discover new targets to delay the initiation and progression of this deleterious disease," Tune says.
Presently, Dr. Tune is working to translate his work in pigs with collaborative studies in obese humans with type 2 diabetes. "At the end of the day," he says, "we're searching for novel ways to improve coronary health in the obese, diabetic heart."
Dr. Tune will discuss his research and what the findings in obese pigs can help researchers understand about heart disease in people when he presents this year's Bowditch Lecture, "Translational Insight Into Regulation of Coronary Blood Flow," on Sunday April 21 at 5:45 PM at the Boston Convention and Exhibition Center.
|Contact: Donna Krupa|
Federation of American Societies for Experimental Biology