Science + Technology

UCLA Study Links Air Pollution to Clogged Arteries

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Got high cholesterol? You might want tostay away from air pollution.

That's the message of a new UCLA studylinking diesel exhaust to atherosclerosis, or hardening of the arteries, whichsignificantly increases one's risk for heart attack and stroke. Published inthe July 26 edition of the online journal Genome Biology, the findings are thefirst to explain how fine particles in air pollution conspire withartery-clogging fats to switch on the genes that cause blood vesselinflammation and lead to cardiovascular disease.

"When you add one plus one, it normallytotals two," said principal investigator Dr. Andr Nel,chief of nanomedicine at the David Geffen School ofMedicine at UCLA and a researcherat UCLA's California NanoSystems Institute. "But we found that adding diesel particles to cholesterol fatsequals three. Their combination creates a dangerous synergy that wreakscardiovascular havoc far beyond what's caused by the diesel or cholesterolalone."

The researchers set up a scenario toinvestigate the interaction between diesel exhaust particles and the fattyacids found in low-density lipoprotein (LDL) cholesterol — the "bad" type ofcholesterol that leads to artery blockage.

In particular, the team was interested inhow oxidation — cell and tissue damage resulting from exposure to moleculesknown as free radicals — contributesto inflammation and artery disease. Free radicals enter the body through smallparticles present in polluted air and are also byproductsof normal processes, such as the metabolic conversion of food into energy.

"Diesel particles are coated in chemicalscontaining free radicals, and the fatty acids in LDL cholesterol generate freeradicals during metabolism in the cells," said first author KeWei Gong, a UCLA cardiology researcher. "We wanted to measure what happens whenthese two sources of oxidation come into contact."

The scientists combined the pollutants andoxidized fats and cultured them with cells from the inner lining of human bloodvessels. A few hours later, the team extracted DNA from the cells for geneticanalysis.

"We saw that the diesel particles andoxidized fats had worked in tandem to activate the genes that promote cellularinflammation — a major risk factor for atherosclerosis," said Dr. Jesus Araujo,UCLA assistant professor of medicine and director of environmental cardiologyat the Geffen School of Medicine.

"The interaction left a genetic footprintthat reveals how interaction between the particles and cholesterol acceleratesthe narrowing and blockage of the blood vessels," Araujonoted.

To duplicate these findings in livingcells, the UCLA team exposed mice with high cholesterol to the diesel particlesand saw activation of some of the same gene groups in the animals' tissue.

"Exactly how air pollutants causecardiovascular injury is poorly understood," Nelsaid. "But we do know that these particles are coated with chemicals thatdamage tissue and cause inflammation of the nose and lungs. Vascularinflammation in turn leads to cholesterol deposits and clogged arteries, whichcan give rise to blood clots that trigger heart attack or stroke."

The researchers' next step will be toconvert the genes' responses to the pollutant-cholesterol combination into abiomarker that will enable physicians to easily evaluate air pollution's effecton health, especially cardiovascular disease.

"Once a biomarker is developed, we'd simplyneed to test a blood sample in order to measure a person's exposure toparticulate matter and determine whether it has reached levels that requiremedical intervention," Araujo said.

The American Cancer Society has reported a6 percent increase in heart- and lung-related deaths for every 10 microgramsper cubic meter rise in particulates.

"Our results emphasize the importance ofcontrolling air pollution as another tool for preventing cardiovasculardisease," Gong said.

The research team included investigators from the fields of nanomedicine, cardiology and human genetics and from theSouthern California Particle Center. Other co-authors included Ning Li, Berenice Barajas and Aldons J. Lusis of the David Geffen School of Medicine at UCLA; WeiZhao and Steve Horvath of the UCLA School of Public Health; Michael Kleinman of the University of California, Irvine; and Constantinos Sioutas of USC.

Grants from the National Institute ofEnvironmental Health Sciences; the National Institute of Allergy and InfectiousDiseases; the National Heart, Blood and Lung Institute; the U.S. EnvironmentalProtection Agency; and the Robert Wood Johnson Foundation supported the study.

-UCLA-

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