Pollution-cholesterol link to heart disease seen

Pollution-cholesterol link to heart disease seen
http://www.latimes.com/news/science/la-me-heart26jul26,0,2928424.story?coll=la-home-center
The combination activates genes that can cause clogged arteries, UCLA researchers say. By Marla Cone, Times Staff WriterJuly 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.
--marla.cone@latimes.com