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BLOOD VESSELS MAKE HEART-DISEASE FIGHTING MOLECULE, U.VA. SCIENTISTS FIND

Researchers are one step closer to harnessing the body's ability to naturally prevent inflammation in heart arteries - a condition that signals hardening of the arteries, or atherosclerosis, which leads to heart attack and stroke. University of Virginia researchers Dr. Klaus Ley and Yuqing Huo collaborated with colleagues at Brigham and Women's Hospital and Harvard Medical School to analyze how this natural anti-inflammatory molecule is produced. The study is published in the August 20 issue of Science magazine.

The new research results indicate that a tiny molecule with a big name - EET, or epoxyeicosatrienoic acid - can turn off the genes that are responsible for vascular inflammation. While more research is needed to find out why and how EET acts and is produced, it is a promising new development in heart disease research.

U.Va.'s co-author Ley said, The enzyme that makes EET was discovered in cells which line the inside of blood vessels. These cells are heavily involved in diseases like atherosclerosis, which affect coronary arteries and in the worst case result in heart attack. They are also involved in angina, a painful affliction that signals that the heart muscle doesn't get enough blood. An enzyme manufactured by the blood cells makes EET, which is a fatty metabolite, also called a lipid.

We already knew that EET opens the blood vessel, but we discovered in this study that it also has anti-inflammatory properties. That means it has implications for fighting atherosclerosis, a disease that begins with inflammation. EET seems to block the key transcription factor that drives a lot of inflammatory genes so they never get switched on.

Ley said that because the presence of EET doesn't last long enough to be analyzed during its normal production cycle in the body, he and co-author Huo infused it intravenously into one of two groups of mice, all of which had developed atherosclerosis. The mouse model was recently engineered at the U.Va. Department of Biomedical Engineering specifically to study the role of inflammatory adhesion molecules in the development of atherosclerosis. As the mice received the intravenous infusion, researchers observed through an intravital microscope the inflammatory cells migrating into what would become an atherosclerotic lesion in the blood vessel wall, and used video recordings with a digital processing system to analyze the cell migration rates.

Manipulating the enzyme that makes EET or the receptor that sees it would be the aim of further research, Ley said. Ley is continuing research on several different bad adhesion molecules that allow atherosclerotic plaque to build up on blood vessel walls, and how the good molecule EET is regulated and connects to cell receptors to stop the adhesion molecules from being expressed.

August 20, 1999