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Zebra Fish May Provide Key to Targeted Angiogenesis

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Zebra Fish  Provide Key to Targeted Angiogenesis

Zebra Fish May Provide Key to Targeted Angiogenesis

December 01, 2004

By: Diana Barnes-Brown for Veins1

A common tropical fish known as the zebra fish seems to have unwittingly provided scientists with revolutionary new information about how to repair blood vessel and nerve damage.

Scientists have started using the zebra fish to help aid them with research on angiogenesis, or the creation of new circulatory structures. The little fishes, found in many pet stores and at-home aquariums, are unique because of their transparent bodies, which allow scientists to see the growth and changes of the fishes’ circulatory systems.

When the blood supply to parts of the body is cut off, severe damage results. For example, if blood supply to heart tissue is stopped, a heart attack results. If blood supply to brain tissue is cut off, stroke, tissue death, and brain damage can result. If blood supply to a limb or organ is stopped (as often happens in crushing injuries), tissue death or gangrene can result, often requiring amputation or removal.

Of specific practical concern in work regarding the circulatory system is the regeneration of blood vessels. Blood vessels are the smallest pathways in the body responsible for carrying “fresh” blood, oxygenated by the lungs, to areas that need it. In understanding how the blood vessels work, an analogy comparing the circulatory system to a roadway is helpful: the large veins and arteries are the “main road,” the wide pathways responsible for helping blood travel to and from the heart and lungs over longer distances, while the blood vessels act as the “driveways” “connector roads” to structures in the body. If the blood vessels are damaged, then blood cannot get to the areas that need it, no matter how well the rest of the circulatory system works.

If scientists can learn to create or control the process that governs blood vessel growth, then it will be possible for doctors to use this knowledge to bring about targeted angiogenesis in areas that desperately need replacement blood vessels after an injury, heart attack, or stroke.

Scientists have also found that nerves orient themselves very specifically toward a target organ or tissue as they grow, and that by means of attraction and repulsion signals, molecules called “signal molecules” guide the nerve cells to the target location.

In the course of experimentation involving various pathways in zebra fish, Monica Autiero and co-researchers under the direction of Peter Carmeliet (of the Flanders Interuniversity Institute for Biotechnology (VIB) and the Catholic University of Leuven) hypothesized that blood vessel growth may follow a the same signals that guide nerve cell growth; if this was the case, and if scientists could learn how to control these signals, new blood vessels could eventually be generated using the same signaling molecules that guided nerve cell growth.

The team of Flemish scientists collaborated with French and American scientists to test this hypothesis by investigating signal molecule receptor UNC5B in zebra fish (the presence of this receptor implies that there are signal molecules that use it). The scientists found that in fish that lacked signal molecule receptor UNC5B, blood vessels formed random, erratic branches and abnormal patterns. This shows that there is a strong connection between the presence of signal molecules and the proper growth and distribution of blood vessels – that is, it is likely that both nerve and blood vessel growth rely on the same chemical/molecular “guides.”

These findings are being hailed as a big step in the move toward laboratory angiogenesis. Scientists are optimistic that the discovery will be instrumental in helping them develop highly targeted angiogenesis techniques to help people with a variety of medical problems.

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