Studies show diesel smog increases chances of deadly blood clots.

Ewen Callaway-
www.nature. com-

Study after study has shown a connection between smoggy days and an
increase in deaths. Now two experiments, one on mice and the other in
men,
clarify why. Diesel fumes, they find, encourage blood clots that can
bring
on heart attacks and strokes.

The study in people helps to prove the correlation between heart
problems
and a city's poor air quality and hints at the role of clotting in
this
process. And the work in mice exposed to smog suggests that the immune
system kick-starts the process.

Together, the two call attention to the dangers of air pollution for
people with heart trouble. "The message we're trying to promote is
please
exercise, it's good for your heart and your health. But if it's a bad
[air] day you should think twice," says David Newby, a cardiologist at
the
University of Edinburgh, UK, who led the clinical study.

Proof Positive

Up to 800,000 people around the world died from causes attributable to
air
pollution in 2000 alone, according to the World Health Organization -
many
through heart attacks and stroke.

To add experiment to observation, Newby's team recruited 20 men who
had
previously had a heart attack. The team exposed half the patients to
diesel exhaust made by a Volvo tractor engine - about equivalent to a
smoggy day in London - while closely monitoring their condition.

After 2 spells of 15-minutes on an exercise bike, the patients who
inhaled
the small amounts of soot showed the strain. Less blood made it to the
muscular tissue of their heart, and levels of a protein called tPA,
which
responds to blood clots, were lowered. After the experiment, these
factors
returned to normal.

"This sort of back-up mechanism [to clotting] is lost when you're
exposed
to diesel, and therefore it makes a clot form a lot more likely to be
successful and a heart attack to occur," says Newby, whose team
reports
the findings in the New England Journal of Medicine1.

Clot Away

Previous work in hamsters identified excessive blood clotting, or
thrombosis, as a culprit. Now a study in mice shows how this happens.

Gökhan Mutlu, a physician at Northwestern University's Feinberg School
of
Medicine in Chicago, and his colleagues were studying the effects of
air
pollution in mice when they noticed that animals exposed to dirty air
didn't bleed for as long as mice that breathed clean air. The
fume-inhaling mice showed higher levels of several proteins linked to
blood clotting.

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When Mutlu's team eliminated immune cells that are likely to mop up
soot
particles from the lungs of mice, no clotting problems occurred. The
same
thing happened in mice that were missing a gene for an immune
signalling
protein called interleukin- 6.

The results suggest that it is the immune response to particles in the
lungs that causes inflammation and leads to clots, they report in the
Journal of Clinical Investigation2.

"These two studies are pretty nicely complementary, " says Mutlu,
referring
to his work and Newby's clinical study.

Cleaner Air

The two studies are convincing, but there could be other explanations
for
how air pollution causes heart attacks, says Benoit Nemery, a
toxicologist
at the Catholic University of Leuven, Belgium. He has shown that tiny
soot
particles enter the bloodstream where they may affect the heart
directly,
rather than via an immune response in the lung.

Nemery agrees that people with heart problems shouldn't run marathons
when
the air is poor, but he sees a better solution than stopping the
exercise:
"I don't think you should blame the victims - that they should change
they
their way of life. What we should aim for is to make the pollution go
down."

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References

1. Mills, N., et al. N Engl J Med 357 , 1075 - 1082 (2007).
http://content. nejm.org/ cgi/content/ abstract/ 357/11/1075

2. Mutlu, G., et al. J Clin Invest doi:10.1172/ JCI30639 (2007).
http://www.jci. org/cgi/reprint/ JCI30639v1. pdf

20 September 2007; | doi:10.1038/ news070917- 10

Stay in if you're having a bad air day

Studies show diesel smog increases chances of deadly blood clots.

Ewen Callaway
http://www.nature. com/news/ 2007/070917/ full/070917- 10.html