Air pollution is a big killer. Researchers estimate that smog—particularly the tiniest particles in the mix—contributes to the early deaths of up to 7 million people worldwide each year. Harm to fog-filled lungs is an obvious concern, yet air pollution is notably linked to cardiovascular events, including heart attacks and stroke. And researchers have puzzled over why.

A leading theory is that the teeny particles may cause systemic inflammation and cellular stress that can wear on the cardiovascular system and muck up heart rhythms. But a new study suggests that the nanoparticles have a more direct role in the disease.

In mice and humans, air-pollution-sized nanoparticles slipped from the lungs and into the blood stream. There, they glommed onto plaques in the arteries of both species, directly contributing to atherosclerosis and deadly cardiovascular diseases, researchers report in an upcoming issue of ACS Nano.

The study, led by cardiovascular scientists at the University of Edinburgh, may help researchers better understand cardiovascular health and figure out ways to minimize the risks of air pollution. The findings may also help manufacturers develop safer products, since nanoparticles can now be tested in everything from electronics to medical equipment and pharmaceuticals.

“These findings have immediate relevance for the nanotechnology industry where a diverse range of engineered nanomaterials is being developed for an ever-increasing number of applications,” the authors write.

Gold rush

Animal data had hinted that nanoparticles can hop the barriers from in the lungs to ride in the bloodstream. But researchers didn't know if that applied to humans. For their new study, the authors recruited 14 healthy male volunteers to breathe in gold nanoparticles of varying sizes for two hours in a chamber where they also did moderate exercise on a stationary bike. The exercise ensured that the participants took deep breaths and got the nanoparticles deep in their lungs.

The gold nanoparticles were similar in size to those found in combustion exhaust, a leading component of air pollution. The finest particulates of air pollution can contain nitrogen oxides, sulfur dioxide, and other toxic ingredients that can induce oxidative stress and inflammation in the body. Gold, on the other hand, is effectively inert.

The researchers took blood and urine samples from the volunteers throughout the first 24 hours after their gold exposure, then again after three months. None of the volunteers had gold in their bloodstream before the experiment. But within 15 minutes gold showed up in some of the participants. After 24 hours, 12 of the 14 had it in their blood. The participants who breathed in the smallest nanoparticles—about 5 nanometers or less in diameter—had gold show up in their urine after 24 hours. The particles could still be detected in both blood and urine after three months.

The researchers next gave doses of gold nanoparticles to mice genetically engineered to develop atherosclerosis (where plaque builds up in their arteries). The gold showed up in their livers and arteries. Most importantly, gold joined into the plaques in the animals’ arteries, contributing to the blood flow blockage.

To see if this happens in humans, the researchers recruited 12 patients scheduled to have surgery to remove plaques from their carotid artery. Three of them agreed to breathe in gold nanoparticles (5 nanometers in diameter) for four hours while resting 24 hours before their surgery. The researchers detected gold in one patient’s blood and the urine of the other two. All three had gold nanoparticles in the plaques removed from their arteries, while none of the other nine patients had signs of gold.

Though the gold nanoparticles seemed to contribute directly to blockages, the authors fear that nanoparticles from pollution would be even worse. Because those particles can be reactive and toxic, they could induce further inflammation and cellular stress when clumped on the side of an artery, exacerbating disease. And if the particles clump at other sites of inflammation in the body, it could have implications for other disease, such as cancer. It could also mean babies may be exposed to nanoparticles during pregnancy.

“A greater understanding of how nanoparticles translocate and accumulate at sites of disease is of paramount importance for the risk assessment of both environmental and engineered nanoparticles,” the authors conclude.

ACS Nano, 2017. DOI: 10.1021/acsnano.6b08551 (About DOIs).