Nicotine study surprises scientists / Substance promotes blood vessel growth, tumors, artery plaque

July 03, 2001|David Perlman, Chronicle Science Editor

In an unexpected finding, Stanford University researchers have discovered for the first time that nicotine can promote the dangerous growth of new blood vessels, increase the growth of tumors and stimulate formation of the artery- clogging substance called plaque.

At the same time, the researchers said, nicotine may ultimately prove useful in treating disorders where blood flow is impaired or new blood vessels are needed.

The drug is now being evaluated by other researchers as a possible treatment for Alzheimer’s and Parkinson’s diseases as well as for pain and sleep disorders.

The newest findings on nicotine’s harmful effects are reported this month in the journal Nature Medicine by a Stanford research team headed by Dr. John P. Cooke, a heart specialist and chief of vascular medicine there.

The drug “is much like fire — it can be very harmful, and yet it can be useful if you know how to control it,” Cooke said in an interview.

Earlier research on smoking had indicated that nicotine prevented or at least limited the formation of new blood vessels, a process known as angiogenesis. Cooke and his team were experimenting with mice to prove that theory when they found the drug had exactly the opposite effect.

“We didn’t expect it,” Cooke said, “but it was a great finding.”

Dr. Rakesh Jain, a Harvard Medical School biomedical engineer who studies the formation of blood vessels, agreed. In a commentary also published in Nature Medicine, Jain called the Cooke team’s results “significant and timely.”

In experiments, the researchers looked at the effects of nicotine in several groups of mice. They implanted tiny plastic disks impregnated with nicotine into one group. They injected the drug into the hind legs of mice whose legs were deprived of normal blood supplies. They implanted lung cancer tumors in a group of mice who then drank nicotine-laced water. And they administered nicotine to a colony of mice who were specially bred to accumulate plaque in their arteries.

When the researchers compared the results of the treated and untreated mice,

they found that:

— New blood vessels formed within the implanted plastic disks.

— The hind legs of mice whose normal blood supply had been cut off developed networks of new blood vessels.

— The tumors in the mice developed fresh blood vessels, and the cancers grew rapidly.

— And finally, plaque grew faster and more thickly in the mouse arteries that were already blocked by the fatty material.

To Cooke the implications of the research are clear: Many people now using nicotine patches or nicotine gum in an effort to curb their smoking may be courting danger from cancer and heart disease if they use their nicotine devices for too long, he said.

There is also a danger that the nicotine they use will promote the growth of tumors if they already have cancer, or that they will develop more plaque in their arteries if they already show signs that plaque formation has begun, he said.

On the other hand, Cooke said, future research may show potential benefits from nicotine where tissues are starved of oxygen and need more blood:

If the brain’s blood supply is impaired, and strokes become possible, for example, the drug might prove useful in improving blood flow there. And where clogged arteries limit blood flow in the legs, nicotine might possibly help to increase the flow. The drug might even prove useful in wound healing, Cooke said.

As a result of the group’s research, Stanford has already patented the use of nicotine to promote the formation of new blood vessels, the university said.

Endovasc Inc., a pharmaceutical research company in Montgomery, Texas, has been granted a license to the patent. Cooke and his colleagues were “inventors of this patent, and might receive royalties from the license,” says a statement accompanying the report in the journal.

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