Leuven, Belgium - When a blood vessel clogs up, a localized deficiency of
oxygen results, causing the surrounding tissue to die. However, working with
mice, VIB scientists connected to the Katholieke Universiteit Leuven have been
able to prevent muscular tissue with severe hypoxia from dying. The muscles seem
to ‘adapt’ to the lack of oxygen - a metabolic tour de force that animals also
use when hibernating, but that has remained a mystery until now. For the medical
world, this discovery signifies an important step forward in limiting damage
after a heart attack, for example, or for better preservation of organs awaiting
transplants.
No life without oxygen - but oxygen can also be harmful
Oxygen is necessary to life. Humans and animals use oxygen to convert fats
and sugars into the energy that keeps all life processes running and maintains
the body’s temperature. At the same time, oxygen can also be harmful when it is
converted into toxic oxygen particles that cause serious damage to tissues and
organs.
What about a little less?
Some animals can survive in places with little oxygen. Birds at high
altitudes, for example, or animals that live underground or that can dive under
water for a long time. Hibernating animals turn their bodily processes down low
and live with a reduced amount of oxygen.
We can detect changes in the amount of oxygen with certain sensors. These
oxygen meters are essential in adapting the body’s metabolism during the
changeover from an oxygen-rich to an oxygen-deficient environment.
Oxygen meter PHD1 plays crucial role
Julián Aragonés, Martin Schneider, Katie Van Geyte and Peter Fraisl - under
the direction of Peter Carmeliet - have studied the role of the PHD1 oxygen
meter. To do this, they used ‘knock-out’ mice that were unable to produce PHD1.
They found that blocking an artery in these mice - thus obstructing the oxygen
supply to the muscle - did not lead to the death of the surrounding muscular
tissue. This was a very surprising result, since the muscle received too little
oxygen to survive under normal circumstances. In the mice lacking the PHD1
oxygen meter, the tissue apparently ‘reprogrammed’ itself by means of a
metabolic shift, so that the muscle needed less oxygen in order to continue to
function. Furthermore, less oxygen in the muscle meant fewer toxic oxygen
particles and thus less damage. So, the muscle could use the little oxygen that
was available in a better and safer manner. These alterations enabled the muscle
to stay perfectly healthy in these normally life-threatening conditions. In
addition, the researchers also demonstrated that treating healthy mice even
briefly with a PHD1-blocker could protect the muscles against oxygen deficiency
- which opens a path to new therapies.
New therapeutic possibilities?
These findings have significant implications for several medical
applications. Scientists can now begin to investigate whether PHD1-blockers can
prevent the damage caused by blockage of a blood vessel through thrombosis or
after a heart attack (in which the cardiac muscle experiences a shortage of
oxygen). New treatment alternatives may also be possible for strokes, and
surgeons may also be able to reduce the oxygen supply to organs for a longer
period of time during many types of operations.
The absence of PHD1 might also explain the mysterious adaptations of
hibernating animals, with important implications for the preservation of organs
for transplant. Such tissues often have to contend with prolonged oxygen
deficiency, which destroys their viability for transplantation. If these organs
could be kept in a ‘hibernation’ condition, perhaps more lives could be
saved...
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Mention both VIB and the university
When reporting this research, please always mention VIB as well as the
university concerned.
This article was originally published in EurekAlert.
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