Diesel Fumes Team Up With Cholesterol for Atherosclerosis

July 27, 2007

LOS ANGELES -- Diesel pollution may induce cardiovascular risk, researchers found in a genome-wide study.

LOS ANGELES, July 27 -- Diesel pollution may induce cardiovascular risk, researchers found in a genome-wide study.

Diesel fumes synergistically link up with cholesterol to activate genes that turn up atherosclerosis and vessel inflammation, according to Andre Nel, M.B.Ch.B., Ph.D., of the University of California, Los Angeles, and colleagues.

In vitro and mouse studies revealed that a low dose of diesel exhaust particles combined with oxidized phospholipids generated in LDL cholesterol upregulated 1,555 genes, of which the most upregulated clusters were in pathways related to vascular inflammation and atherosclerosis, they reported in the July 26 issue of Genome Biology.

Of the upregulated genes, 43% exhibited synergy when the diesel particles and oxidized phospholipids were combined.

"Our gene-expression data are of considerable importance in understanding how ambient air pollution might contribute to endothelial injury and to atherosclerosis," they wrote.

Air pollution, particularly ambient particulate matter, has been associated with increased cardiovascular morbidity and mortality in previous studies, although the mechanism has been debated.

But, "it is becoming increasingly clear that particulate matter exerts pro-oxidative and pro-inflammatory effects in the lung that can also spill over to the systemic circulation," they added.

The researchers conducted a series of experiments to clarify how the process occurred. They first looked at heme oxygenase-1, an important oxidative stress sensor in endothelial cells.

They found that human microvascular endothelial cells had a 15-fold higher density of this protein when treated with diesel exhaust particles plus phospholipid oxidation products than when treated with diesel exhaust particles alone and five-fold more than when treated with phospholipid oxidation products alone.

Then, they assessed gene-expression profiles using microarrays and found that at total of 1,555 genes were significantly upregulated by at least 1.5-fold (P

The mice exposed to the ultrafine, mostly diesel particles, had significantly upregulated genes for heme oxygenase-1, the oxidative stress sensor in endothelial cells, as well as for two key unfolded protein response gene transcription factors compared to the other three groups of mice (P