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 hy 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 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, MD,
PhD, 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, MD, 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.
Coauthors
are Margaret E. Haberland, PhD; Ming-Len Jien, BS; Diana M. Shih,
PhD; and Aldons J. Lusis, PhD. 
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