UW News

November 4, 2004

Investigating cholesterol oxidation and artery disease

Some functions of the human body that worked effectively for survival when people had short life spans, living only long enough to reproduce and raise their young, may have long-term consequences that catch up with us as we live longer lives.

One of those functions is inflammation, a specific response to an injury that brings white blood cells to the site and begins a process of healing. Inflammation is also a common aspect of response to diseases, such as respiratory viruses.

But inflammation can also become a chronic process, and the effects of long-term inflammation, especially over longer and longer lifetimes, are now being studied in relation to several diseases that afflict an older population.

Dr. Jay Heinecke, UW professor of medicine in the Division of Metabolism, Endocrinology and Nutrition and holder of the Karasinski Chair in Metabolic Research, has been concentrating on the relationship between inflammation and the development of atherosclerosis, sometimes called hardening of the arteries.

He will speak on “Lipoprotein Oxidation in Atherogenesis: The Good, the Bad or the Ugly?” at noon on Thursday, Nov. 18, in room T-625 of the Health Sciences Center. The lecture, open to everyone, is part of the Science in Medicine series, sponsored by the School of Medicine’s Office of Research and Graduate Education.

“Although many people think of cholesterol as the problem,” Heinecke said, “it’s clear that LDL cholesterol has to be modified to be taken up by macrophages in the artery wall. Oxidation may be one important form of modification. Macrophage cholesterol accumulation is what marks the development of atherosclerosis.”

Heinecke’s laboratory is particularly focused on understanding these oxidative reactions in relation to both LDL (known as the bad type) and HDL (known as the good) cholesterol. Evidence suggests, he said, that the good cholesterol is also affected by oxidative reactions that may limit its ability to slow down the development of artery disease.

Oxidative reactions are necessary for life, he said, and it may be hard to pinpoint where these needed functions cross over into chronic oxidative stress. He suggested, though, that he and other researchers are looking at other conditions such as osteoarthritis and even Alzheimer’s disease in relation to long-term oxidative stress.

“We have strong evidence that specific oxidants are important for certain pathways,” he said. “I don’t think that people who are counting on one antioxidant to take care of all these different processes are going to be successful.”

His lab is studying oxidative reactions with a number of advanced techniques, including mass spectrometry, high-performance liquid chromatography and high-resolution nuclear magnetic resonance spectroscopy.

Heinecke earned his M.D. degree from Washington University in St. Louis in 1981 and then came to the UW for a residency in internal medicine. He was also a postdoctoral fellow in the Division of Metabolism, Endocrinology and Nutrition and then a senior fellow in the UW Department of Biochemistry from 1987 until 1990.

He was a faculty member at Washington University in St. Louis from 1991 until 2002, when he was professor of medicine and professor of molecular biology and pharmacology there.

In 2002, he returned to the UW to take his current position. He also directs the Mass Spectrometry Resource in the Department of Medicine and is an attending physician at UW Medical Center.

He has received numerous awards, including the American Heart Association’s Jeffrey M. Hoeg Arteriosclerosis, Thrombosis and Vascular Wall Biology Award in 2001 and an Excellence in Mentoring Award from the Washington University Graduate Student Senate in 2002. He is a member of several editorial boards, including the Journal of Clinical Investigation, the Journal of Lipid Research and the Journal of Biological Chemistry.