A new US study suggests that diesel exhaust particles in air pollution combine with artery clogging "bad" cholesterol to increase a person's risk of cardiovascular disease. Working together, the two substances switch on genes that cause inflammation of artery walls that eventually harden (causing atherosclerosis) and make it more likely that the person will suffer a heart attack or stroke.

The study is published in the journal Genome Biology and is the work of scientists at the University of California in Los Angeles (UCLA).

Leading the research was Dr André Nel, chief of nanomedicine at the David Geffen School of Medicine at UCLA and researcher at UCLA's California NanoSystems Institute. Nel said when the diesel particles combined with blood fats, their impact was stronger than their individual effect.

"When you add one plus one, it normally totals two," said Nel.

"But we found that adding diesel particles to cholesterol fats equals three. Their combination creates a dangerous synergy that wreaks cardiovascular havoc far beyond what's caused by the diesel or cholesterol alone," he added.

The researchers said their findings could explain why hospitals admit more cases of heart disease, and more people die from it, when air pollution goes up.

Previous studies have suggested links between a rise in airborne particles and increased deaths from heart disease. The American Cancer Society for example estimates that for every 10 micrograms per cubic meter rise in air particulates heart and lung related deaths go up by 6 per cent.

When blood fats like the fatty acids found in low-density lipoprotein (LDL) or "bad" cholesterol get stuck in artery walls they fall prey to free radicals givng away oxygen and they become oxidized (the same way iron becomes rusty) and this makes the artery walls become stiff and narrow. This is the start of atherosclerosis, which increases the risk of heart attack and stroke from blood clots.

However, scientists have for some time suspected that air pollutants, such as the very small particles present in diesel exhaust fumes, accelerate this process in some way. Experiments in mice have confirmed it.

Free radicals have at least two routes to enter the blood. They stick to very small particles, such as those in diesel fumes found in polluted air which is breathed in, and they are also a natural by-product of metabolism and food digestion.

Lead author of the study and researcher in cardiology at UCLA, Ke Wei Gong said that:

"We wanted to measure what happens when these two sources of oxidation come into contact."

Nel and colleagues took human microvascular endothelial cells (HMEC), these are cells from artery walls, and conducted three experiments. One where the HMEC cells were exposed to diesel exhaust fumes only, another where the HMEC cells were exposed only to oxidized blood cholesterol fats, and a third where the cells were exposed to both.

They then extracted the DNA from the cells in all three experiments and analysed the genetic changes.

They found that the diesel particles and blood cholesterol fats together had a much greater effect than either of them separately.

UCLA assistant professor of medicine and director of environmental cardiology at the Geffen School of Medicine, Dr Jesus Araujo explained:

"We saw that the diesel particles and oxidized fats had worked in tandem to activate the genes that promote cellular inflammation; a major risk factor for atherosclerosis."

"The interaction left a genetic footprint that reveals how interaction between the particles and cholesterol accelerates the narrowing and blockage of the blood vessels," said Araujo.

The team then replicated the findings in living cells using laboratory mice with high cholesterol. They found that the same group of genes were activated.

The researchers said they don't know exactly how air pollutants damage the arteries, but as Nel explained:

"We do know that these particles are coated with chemicals that damage tissue and cause inflammation of the nose and lungs. Vascular inflammation in turn leads to cholesterol deposits and clogged arteries, which can give rise to blood clots that trigger heart attack or stroke."

Nel and colleagues are continuing with the project. They hope to develop a biomarker test that doctors can use to evaluate the effect of air pollution on health, especially with respect to cardiovascular disease.

Araujo explained that:

"Once a biomarker is developed, we'd simply need to test a blood sample in order to measure a person's exposure to particulate matter and determine whether it has reached levels that require medical intervention."

The researches said their findings emphasized the importance of controlling air pollution as another way to fight the rise in cardiovascular disease.

"Air pollutant effects on endothelial cells."
Gong KW, Zhao W, Li N, Barajas B, Kleinman M, Sioutas C, Horvath S, Lusis AJ, Nel AE, Araujo JA.
Genome Biology, 2007, 8:R149
doi:10.1186/gb-2007-8-7-r149
Published online 26 July 2007

Click here for Abstract.

: Catharine Paddock

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