Tags: Gene | Triggers | Healthy | Blood | Vessel | Growth

Gene Triggers Healthy Blood Vessel Growth

Sunday, 30 September 2001 12:00 AM

The growth of new, healthy blood vessels is critical in treating people suffering from heart attacks, diabetes, and wounds that refuse to heal -- all ailments characterized by a lack of blood and oxygen to the affected area.

Now, researchers have shown that mice genetically engineered to make higher-than-normal amounts of a protein dubbed HIF-1 alpha in their skin have 66 percent more blood vessels in equivalent volumes of tissue than do mice that were not genetically engineered.

The new blood vessels are of about the same diameter and shape as normal capillaries, but closer together, said researcher Jeffrey M. Arbeit of the University of California, San Francisco. The genetically engineered mice have red ears and red skin because of the dense blood vessels. He and his colleagues reported their work in the October issue of the journal Genes and Development.

"This is a very well done study," Judah Folkman of Children's Hospital in Boston told United Press International. "No one yet knows what the best way is to turn on blood vessel growth but HIF-1 looks promising."

Many other compounds that induce blood vessel growth also make blood vessels more permeable, leading to the kind of swelling a person might see after a bee sting or mosquito bite.

"The really striking aspect of this work," Arbeit said, "is that the blood vessels in the HIF-1 alpha mice did not leak."

The blood vessels of the HIF-1 alpha mice were also no more likely to leak after the researchers applied an inflammatory treatment to the animal's ears than were blood vessels in normal mice, he told UPI. (Blood vessels in mouse ears are close to the skin, and tend to leak if researchers spread mustard oil on the animal's ears.)

Previous work has shown that mice genetically engineered to produce higher than normal amounts of vascular endothelial growth factor, or VEGF, have leakier blood vessels than normal mice do. They VEGF mice also have leakier blood vessels than do the HIF-1 mice.

The lack of leakiness is important in finding ways to grow new blood vessels normally, and in designing therapies for people who are not getting enough blood to their hearts, limbs, or wounds, said Gregg Semenza of The Johns Hopkins University in Baltimore, whose laboratory discovered HIF-1. He cautions, however, that findings in animal models are not always directly applicable to people.

The HIF-1 alpha protein is part of a larger protein called hypoxia-inducible factor 1, or HIF-1. This protein, which is made by cells experiencing oxygen deprivation, or hypoxia, regulates the activity of several genes that promote the growth of new blood vessels.

HIF-1 also regulates genes involved in a number of other cellular processes, including helping cells get energy from sugar, Arbeit told UPI. This raises the possibility that HIF-1 alpha might "potentially rev up the metabolic machinery to support an increase in cell [growth] necessary to cover a wound or heal a heart," he said. Arbeit cautioned, however, that further experiments need to be done to test this idea.

Copyright 2001 by United Press International. All rights reserved.

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The growth of new, healthy blood vessels is critical in treating people suffering from heart attacks, diabetes, and wounds that refuse to heal -- all ailments characterized by a lack of blood and oxygen to the affected area. Now, researchers have shown that mice...
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2001-00-30
Sunday, 30 September 2001 12:00 AM
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