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Stimulant. Nicotine led to new blood vessels (arrows, right) in these mouse tumors, while a placebo didn't (left).

Nicotine Grows New Blood Vessels

Nicotine, the addictive ingredient in tobacco smoke, is used in nicotine replacement therapy to help smokers kick the habit, and is being considered as a treatment for diseases such as Alzheimer's and Parkinson's. But a study published in the July issue of Nature Medicine shows another dangerous side of nicotine: At concentrations found in the blood of smokers, nicotine promotes the growth of new blood vessels, or angiogenesis, which is believed to stimulate tumor growth.

Cardiologist John Cooke and colleagues from Stanford University in Palo Alto, California, added nicotine to cultured human endothelial cells, the cell type that lines blood vessels. Nicotine stimulated their growth and caused them to form small, blood-vessel-like tubes. They then tested the effects of nicotine in four mouse models of disease: an ischemia model, where they cut off blood flow to one of the hind legs, an inflammation model, in which a polyvinyl disc was implanted under the animal's skin, a lung cancer model, and an atherosclerosis model, where cholesterol plaques clog blood vessels.

In all cases, they found that nicotine caused new blood vessels to grow into the affected area. These spurred the growth of tumors in the cancer model and plaques in the atherosclerosis model. "We were surprised that [nicotine] enhanced angiogenesis," Cooke says. "We made the mistake of equating nicotine to tobacco," which overall reduces the growth of blood vessels, he notes. The results suggest caution in using nicotine treatment, Cooke says, because it might promote cancers or cardiovascular disease. On the other hand, nicotine may well be useful for speeding up wound healing, when growth of blood vessels is just what's needed.

"The results are intriguing," says cancer researcher Rakesh Jain of Harvard Medical School in Boston, Massachusetts. But other studies seem to contradict the outcomes, he says; for instance, nicotine has no effect on blood vessel growth in the developing chick and does not raise the risk of heart attack in patients with heart disease. And as for smoking, the picture is even more complicated, because nicotine is only one of about 4000 chemicals in cigarette smoke, Jain notes, some of which injure blood vessels.

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The Cooke lab