A new US study has suggested an explanation for how the small particles in air pollution caused by traffic and industry might trigger blood clots and cause heart attacks and strokes.

The study is reported in the September online first issue of the Journal of Clinical Investigation and is the work of Dr Gökhan M Mutlu of the University Feinberg School of Medicine, Chicago, Illinois, and colleagues.

Mutlu and colleagues said that by studying the effects of small air pollution particles in mice, they have disovered how air pollution that makes the lungs inflamed causes cardiovascualr disease and death.

While scientists already know there is a link between small particles in air pollution and elevated risk of cardiovascular events such as heart attacks and stroke, the underlying mechanism is still a mystery.

Recent studies on animals and humans suggest that the small particles affect hemostasis, the various methods by which blood is maintained in a fluid state.

In this study on laboratory mice, the researchers investigated how small particles might accelerate thrombosis.

The results showed that mice whose lungs were injected with a saline containing particles smaller than 10 micrometres, one tenth of the thickness of a strand of hair, had a shorter bleeding time and shorter plasma clotting times and increased levels of various clotting agents such as fibrinogen and factor X.

The particles were collected by the Environmental Protection Agency from samples of polluted air.

The increase in clotting factors coincided with increases in clotting events such as generation of thrombin in the blood vessels, and an acceleration of arterial thromboism and also coincided with an increase in the immune system agent interleukin-6 in the alveoli of the lungs (little sacs where oxygen passes into the bloodstream).

24 hours later, the level of IL-6 had gone up 15-fold. This spike could explain why spikes in air pollution are closely followed by significant increases in heart attacks within 24 hours.

When they suppressed the immune cells that attack foreign substances and release IL-6 (called macrophages) in the alveoli by injecting with liposomal clodronate, the clotting stopped.

Also, mice that had their immune systems suppressed so it did not release IL-6 were protected against the particle triggered clotting events.

This strongly suggested that IL-6 was the driving force.

The scientists concluded that:

“Our findings suggest that exposure to particulate matter triggers IL-6 production by alveolar macrophages, resulting in reduced clotting times, intravascular thrombin formation, and accelerated arterial thrombosis.”

“These results provide a potential mechanism linking ambient particulate matter exposure and thrombotic events,” they added.

Mutlu and colleagues are now working on a study to see if the clotting effect of IL-6 can be counteracted by low dose aspirin, which has been shown to thin the blood and is already used to treat people with heart conditions.

“Ambient particulate matter accelerates coagulation via an IL-6 dependent pathway.”
Gökhan M. Mutlu, David Green, Amy Bellmeyer, Christina M. Baker, Zach Burgess, Nalini Rajamannan, John W. Christman, Nancy Foiles, David W. Kamp, Andrew J. Ghio, Navdeep S. Chandel, David A. Dean, Jacob I. Sznajder, and G.R. Scott Budinger.
J. Clin. Invest., Sep 2007
doi:10.1172/JCI30639

Click here for Abstract.

Written by: Catharine Paddock