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*From the Los Angeles Times*
Pollution-cholesterol link to heart disease seen The combination activates
genes that can cause clogged arteries, UCLA researchers say.
By Marla Cone
Times Staff Writer

July 26, 2007

Strengthening the link between air pollution and cardiovascular disease, new
research suggests that people with high cholesterol are especially
vulnerable to heart disease when they are exposed to diesel exhaust and
other ultra-fine particles that are common pollutants in urban air.

Microscopic particles in diesel exhaust combine with cholesterol to activate
genes that trigger hardening of the arteries, according to a study by UCLA
scientists to be published today.

"Their combination creates a dangerous synergy that wreaks cardiovascular
havoc far beyond what's caused by the diesel or cholesterol alone," said Dr.
André Nel, chief of nanomedicine at the David Geffen School of Medicine at
UCLA and a researcher at UCLA's California NanoSystems Institute. He led a
team of 10 scientists who conducted the study, published in an online
version of the journal Genome Biology.

Although diet, smoking and other factors contribute to the risk of
cardiovascular disease — the leading cause of death in the Western world —
scientists have long believed that air pollution, particularly tiny pieces
of soot from trucks and factories, plays a major role, too.

For years, scientists around the world have reported that on days when
fine-particle pollution increases, deaths from lung diseases, heart attacks
and strokes rise substantially. Riverside County and the San Gabriel Valley
have among the worst fine-particle pollution in the nation.

The scientists say their study, conducted on human cells as well as on mice,
is the first to explain how particulates in the air activate genes that can
cause heart attacks or strokes.

The researchers exposed human blood cells to a combination of diesel
particles and oxidized fats, then extracted their DNA. Working together, the
particles and fats switched on genes that cause inflammation of blood
vessels, which leads to clogged arteries, or atherosclerosis.

The team then duplicated the findings in living animals by exposing mice to
a high-fat diet and freeway exhaust in downtown Los Angeles. The same
artery-clogging gene groups were activated in the mice.

The scientists reported that diesel particles may enter the body's
circulatory system from the lungs, and then react with fats in the arteries
to alter how genes are activated, triggering inflammation that causes heart
disease.

Other research has shown similar inflammatory damage in lungs exposed to
fine particles. Diesel exhaust has also been linked to lung cancer, asthma
attacks and DNA damage.

"Our results emphasize the importance of controlling air pollution as
another tool for preventing cardiovascular disease," said Ke Wei Gong, a
UCLA cardiology researcher who was one of the study's authors.

In many urban areas, including the Los Angeles region, ultra-fine particles
are the most concentrated near freeways, mostly from diesel exhaust, which
is spewed by trucks, buses, off-road vehicles and other vehicle engines.

For decades, California and local air-quality regulators have been
ratcheting down particulate emissions from trucks and other sources, but the
airborne levels in most of the Los Angeles region still frequently exceed
federal health standards.

"There are a few hot spots throughout the country that compete with Los
Angeles from time to time, but in general, we tend to have the highest
levels here," Nel said.

Exposed in a mobile laboratory moving down the freeway, the mice breathed a
concentration of fine particles, 362 micrograms per cubic meter of air. That
was five times higher than the peak that people in the San Gabriel Valley
were exposed to last year.

However, humans breathe polluted air every day for decades, whereas the mice
in the study were exposed five hours per day, three days per week, for eight
weeks.

"The levels were high, but they came from real freeway exhaust so they were
not artificially high," Nel said. "It was almost within the realm of what we
are exposed to."

Diesel particles contain free radicals, which damage tissues, and so do the
fatty acids in cholesterol.

The study aimed to find out what happened when these two sources of
oxidation came in contact.

In the cells exposed to just the cholesterol or just the diesel, the effects
on the genes were much less pronounced. More than 1,500 genes were turned
on, and 759 were turned off, when diesel particles were combined with the
fats.

"Now that we see this genetic footprint, we have a better understanding of
how the injury occurs due to air pollution particles," Nel said.

The UCLA scientists hope to transform the gene changes to a biomarker, which
experts can then use to predict which people are most susceptible to heart
disease from air pollution.

The smaller the particle, the more harm it can cause. More artery-clogging
genes were activated in mice exposed to the ultra-fine particles in diesel
exhaust than in those exposed to larger particles in the air. Smaller
particles generally come from sources of combustion — mostly vehicles.

-- 
www.michaelbalter.com

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Michael Balter
Contributing Correspondent, Science
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