LIAI launches new division to look at novel approaches to heart disease and inflammation

September 30, 2008

While cholesterol-lowering drugs and new technologies have significantly advanced the nation's battle against heart disease, it continues to rank as the No. 1 killer of U.S. men and women. But if researchers at the La Jolla Institute for Allergy & Immunology (LIAI) have their way, the body's immune system will become an important player in reducing heart disease.

"The statins (cholesterol-lowering drugs) have taken a big chunk out of the numbers of people who suffer from heart disease and heart attacks," said Klaus Ley, M.D., director of the Institute's recently launched Inflammation Biology Division. "We hope we can bite off another chunk by controlling the impact of inflammation-causing immune cells on the artery wall."

Mitchell Kronenberg, Ph.D., LIAI president & scientific director, said the Institute recruited Dr. Ley, one of the leading research experts in the field, to head the new division. "We are excited to have a scientist of Dr. Ley's stature lead our new Inflammation Biology Division," he said. "Its creation puts us in a very select group of immunology institutions worldwide that are exploring new ways of fighting heart disease using the immense power of the immune system."

Ley said the immune system's role in heart disease is a relatively recent finding, with the first inklings of its importance discovered in the early 1980s. Prior to that time, scientists believed that atherosclerosis, a blockage in the arteries and the underlying cause of most heart problems, was due to plaque formation caused solely by cholesterol buildup. "The scientific community used to think cholesterol alone led to plaque formation," Ley explained. "While it is true that cholesterol plays a major role, it is not the whole story."

Ley, an internationally recognized scientist who helped pioneer the scientific discipline of vascular immunology, which looks at novel immune-based approaches to heart disease, said inflammation caused by the immune system is also an important participant in plaque formation and weakening of the artery wall. As such, it offers a whole new therapeutic avenue for potential ways to combat heart disease.

Prior to joining the Institute, Ley was director of the Robert M. Berne Cardiovascular Research Center at the University of Virginia, where he oversaw the efforts of the Center's faculty while also conducting his own research program. Ley was recently selected as the 2008 recipient of the prestigious Marie T. Bonazinga Research Award from the Society for Leukocyte Biology. Ley will receive the award in November in recognition for his work illuminating the basic cellular mechanisms underlying inflammation, particularly as it relates to heart disease.

Mark Ginsberg, M.D., a distinguished professor of medicine at UC San Diego and member of the University's new Institute of Engineering in Medicine, which Ley recently joined as an adjunct faculty member, said he is delighted to welcome someone of Ley's achievements as a colleague.

"Klaus' extraordinary contributions to our understanding of inflammation in the vessel wall are a superb complement to existing strengths at UCSD in biomedical engineering, vessel wall biology and other areas related to cardiovascular disease," said Ginsberg, a prominent vascular biology researcher. "LIAI has shown great vision in recruiting Klaus to lead a program to bridge immunology to cardiovascular disease."

In the 1980s, Ley said immunology's role in heart disease first came to light when immunology researchers found that plaque buildup in the arteries also contained inflammation-causing T cells of the immune system. "This opened up the possibility that the inflammatory process was important in heart disease," said Ley. Further study found that inflammatory T cells not only contributed to plaque formation, but they also played a key role in the rupture of the artery wall, which produces a heart attack.

It is this aspect of the inflammatory process that draws Ley's primary attention. He focuses on macrophages, white blood cells of the immune system that usually rid the body of worn-out cells. However, in the case of the artery wall, the macrophages take on a destructive role, exacerbating the weakening of the artery wall caused by plaque formation. "The macrophages switch on a very specific program that we are trying to understand and to decipher why it weakens, rather than heals, the artery wall," said Ley, noting that the macrophages weaken the wall to the point of rupturing, which produces a heart attack. "We believe if we can stop that process, we can stop the rupture," said Ley. "This would have major implications for combating heart disease."

Kronenberg said Ley's work holds great promise. "Up to now, it has been under appreciated how important different types of white blood (immune) cells are in contributing to the leading killer of Americans," said Kronenberg. "Klaus (Ley) is a pioneer whose work is showing that the immune system plays a central role in heart disease."

La Jolla Institute for Allergy and Immunology

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