July 5, 2000 DALLAS, July 4, 2000 - Why can some people eat a high-fat diet without developing the fatty deposits in their blood vessel walls that lead to heart disease, and others can't? One answer may be a gene that causes blood vessels to secrete a protective protein, researchers report in today's Circulation: Journal of the American Heart Association.
"The study suggests why some people are prone to blockages in their coronary arteries and some aren't," says Weibin Shi, M.D., Ph.D., a researcher at the University of California, Los Angeles Department of Medicine.
Researchers at UCLA studied cells from the endothelium, or blood vessel lining, of the aortas of two different strains of mice. One strain was a type of mouse that tends to develop atherosclerosis when fed a high-fat diet, while the other type resists developing the disease despite such feeding. The aorta is the body's main artery and carries blood from the left ventricle of the heart to other arteries.
In humans as well as mice, a high fat diet increases blood levels of low-density lipoprotein (LDL), the "bad" cholesterol that at high levels is associated with an increased risk of atherosclerosis. Because the early stages of atherosclerosis are similar in mice and in humans, these findings may hold important implications for humans as well.
Researchers exposed the endothelial cells to mildly oxidized human LDL. Oxidized LDL is known to cause the cells of the endothelium to produce proteins that contribute to atherosclerosis.
After exposure to oxidized LDL, cells from the atherosclerosis-susceptible mice produced proteins that contribute to atherosclerosis, while cells from the atherosclerosis-resistant mice produced a protein called HO-1 that scientists believe inhibits the disease.
"The study has important implications for treatment," Shi says. "We may be able to block the pathways that contribute to the disease, or stimulate others that interrupt it."
In an accompanying editorial, Jan L. Breslow, M.D., of Rockefeller University wrote that the study is the first direct proof that factors in the blood vessel wall, that are independent of diet, are involved in atherosclerosis development.
"These results may provide clues to understanding atherosclerosis susceptibility in humans," Breslow wrote. The study provides a huge boost for atherosclerosis research: a new, previously unknown factor in development of the disease and a new tool with which to study it. It also opens the door for the development of new tests to help determine atherosclerosis susceptibility, and for new treatment methods.
Studies of this newly recognized factor in atherosclerosis susceptibility have yet to be conducted in humans, Shi says.
Co-authors are Margaret E. Haberland, Ph.D.; Ming-Len Jien, B.S.; Diana M. Shih, Ph.D.; and Aldons J. Lusis, Ph.D.
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