Medical Breakthrough For Organ Transplants And Cardiovascular Diseases

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Medical Breakthrough For Organ Transplants And Cardiovascular Diseases

ScienceDaily (Jan. 8, 2008) — 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, Schneider, Van Geyte and Fraisl - under the

direction of 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...

Adapted from materials provided by VIB, Flanders Institute for Biotechnology.

http://www.sciencedaily.com/releases/2008/01/080106193142.htm

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