Netrin-1 Protein not only aids nerve development, but promotes blood vessel growth, too

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Protein not only aids nerve development, but promotes blood vessel

growth, too

02 Nov 2004

http://www.medicalnewstoday.com/medicalnews.php?newsid=15765

A protein important to nerve development serves the dual purpose of

stimulating the growth of blood vessels, researchers from the University

of Utah School of Medicine and Stanford University have discovered. The

discovery opens the possibility that blood vessel growth (angiogenesis)

one day may be induced, or stymied, for therapeutic use against heart

disease, cancer, and other illnesses, according to Dean Y. Li, M.D.,

Ph.D., associate professor of internal medicine in the U of U School of

Medicine's Division of Cardiology. Li is corresponding author of an

article that details the findings to be published next week in the

Proceedings of the National Academy of Sciences online.

The study focuses on Netrin-1, part of the netrin family of proteins,

one of four major classes of neural guidance " cues " that induce axons,

or nerve fibers, to extend in specific directions during development.

Recent evidence has indicated that the other three classes of neural

guidance cues--ephrins, semaphorins, and slits--function as angiogenic

regulators. But until now, netrins had not been shown to have a part in

blood vessel formation.

Nerves and blood vessels often follow parallel paths of development,

which suggests that common cues may induce both processes. In tissue

cultures and animal models, Li and the other researchers showed that

Netrin-1 " stimulates proliferation, induces migration, and promotes

adhesion of endothelial cells and vascular smooth muscle cells. "

" It makes sense that factors that guide nerves also guide blood vessel

growth, " Li said. " This work indicates that there is an expanding number

of signals that regulate vessel growth or angiogenesis. Identifying

these signals and their interaction are critical steps required for

manipulating, blocking, or stimulating blood vessel growth for

therapeutic purposes. "

The researchers' data demonstrate that Netrin-1 is a neural guidance cue

with the " unique ability to attract both blood vessels as well as axons,

and is capable of functioning as a vascular growth factor, " they write.

Understanding what factors induce blood vessel growth could have

important implications for treating disease in the future.

Tumors, for example, depend on blood vessels to supply critical

nutrients to grow. If blood vessel growth in tumors could be stopped, it

may help fight cancer.

Conversely, inducing blood vessel growth may help people with ischemic

heart disease whose hearts don't get enough blood.

Although the discovery about Netrin-1 shows promise, therapeutic

starting or stopping of blood vessel growth to cure human disease is at

least 15 years away--if it proves viable, Li said.

Li began studying whether Netrin-1 promotes blood vessel growth after

discovering a vascular receptor for another neural guidance factor.

Next, he wants to look at the roles of other netrins in blood vessel

development and identify the receptors required for the vascular effects

of Netrins.

Along with Li, other researchers on the project included Kye Won Park,

Dana Crouse, Satyajit Karnik, and Lise K. Sorensen, the U of U School of

Medicine's Program in Human Molecular Biology and Genetics; J.

, U of U Department of Cardiology; Mark Lee and Calvin J. Kuo,

Stanford University School of Medicine.