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Both types of mice were then exposed to either whole diesel exhaust containing particles at a concentration of about 1 milligram per cubic meter, or to filtered outdoor air, for six hours per day five days a week. The rest of the time they breathed filtered air in their cages. Effects of the exposure were measured after two weeks, five weeks and eight weeks of the exposures.
Though some blood vessel growth and chemical changes could be seen in the mice after two weeks of exposure, "generally, the longer the exposure, the more effects we could see," said Sun, also an investigator in Ohio State's Davis Heart and Lung Research Institute. "It's difficult to translate outcomes from an animal study directly to the human experience, but the bottom line is, the shorter the exposure to diesel exhaust, the better."
The exposure to diesel exhaust caused a six-fold increase in new blood vessel formation in the ischemic hind limbs after eight weeks and a four-fold increase in vessel sprouting in the normal hind limbs of the mice in the same amount of time, compared to mice breathing filtered air.
The researchers also saw significantly more blood vessel growth in the implanted cells and in rings of tissue taken from the aortas of mice exposed to the exhaust compared to the control mice exposed to clean air. In fact, the researchers found that three types of blood vessel development occurred in these areas after exposure to the diesel exhaust: angiogenesis, the development of new capillaries; arteriogenesis, the maturation or re-started growth of existing vessels; and vasculogenesis, the formation of new blood vessels.
All of these processes are associated with tumor growth, but unprogrammed angiogenesis in particular can wreak havoc in the human body, Sun said.
"Whenever you talk about a solid tumor, angiogenesis is one of the fundamental mechanisms behind its development. Angiogenesis provides the means for tumor cells to grow because they have to have a blood supply. Without a blood supply, solid tumors will not grow," he said.
"We want our bodies to generate new blood vessels only when we need them. And then stop producing them when we need them to stop."
Though the researchers have not defined every mechanism behind these processes, they sought to explain at least a few ways in which blood vessels are able to sprout or mature after exposure to diesel exhaust.
They observed that diesel exhaust exposure activated a chemical signal, vascular endothelial growth factor, which has long been associated with new blood vessel development. The exposure also increased levels of a protein, hypoxia-inducible factor 1, that is essential to blood vessel development when oxygen levels are low. At the same time, the presence of the exhaust lowered the activity of an enzyme that has a role in producing substances that can suppress tumor growth.
The scientists also tracked low-grade inflammation in tissues exposed to the exhaust, which is often associated with tumor development.
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