NEW YORK (Reuters Health) - In findings that suggest a new theory on how smoking causes disease--and raise concerns about long-term use of nicotine replacement therapy--California scientists have discovered that nicotine can trigger the growth of new bloo

In experiments with human cells and mice, researchers at Stanford University found that nicotine prompted new blood vessel formation--a process believed to help tumors and artery-clogging plaques thrive and grow. They report the findings in the July issue of the journal Nature Medicine. ``This is the first evidence that nicotine promotes angiogenesis, and more work is needed to understand how it is related to tobacco-related diseases,'' lead researcher Dr. John P. Cooke said in an interview with Reuters Health. What it does suggest, he said, is that nicotine-replacement therapy should remain only a short-term therapy to get smokers off of cigarettes--and not a long-term fix for nicotine craving. Considering smoking's untoward effects on arteries, the fact that nicotine would actually promote blood vessel formation seems counterintuitive at first, according to Cooke. ``We started with the opposite hypothesis,'' he said, explaining that his team expected nicotine would injure blood vessels, rather than cause new ones to sprout. Instead, nicotine showed angiogenic effects in experiments with cell cultures and in mice made to develop artery-clogging plaques and models of cancer. Scientists believe that in cancer, new blood vessels emerge to help tumors grow and spread. And, Cooke said, there is now ``good evidence'' that the fatty deposits that clog arteries and lead to heart attack and stroke need the support of tiny, new vessels to thrive. Although it is unclear what nicotine does when it is delivered via a cigarette, Cooke said it is possible that inhaled nicotine helps spur cancer and heart disease through angiogenesis. While that idea is still ``speculation,'' he added, a more immediate concern is that people on nicotine replacement therapy not stay on it longer than recommended--since nicotine on its own may have health consequences. ``This shouldn't be taken to say that nicotine replacement therapy should be stopped,'' Cooke stressed. ``But it should be used only in the short-term.'' A researcher at Harvard Medical School in Boston, Massachusetts, said that these findings are indeed probably most significant in the area of nicotine replacement therapy. ``We're not trying to alarm people using nicotine replacement therapy,'' Dr. Rakesh K. Jain told Reuters Health. For one, he noted, a study of patients with heart disease showed that using the nicotine patch did not raise their risk for heart attack. Instead, Jain said, these ``very preliminary'' findings highlight the need for tracking any long-range effects nicotine replacement therapy might have. But Jain, who wrote an editorial accompanying the report, expressed doubt that smokers are promoting new blood vessel growth through their habit. He pointed out that tobacco smoke contains thousands of chemicals, some of which are clearly injurious to blood vessels. The vessel-promoting effects of nicotine, he said, ``are probably wiped out by tobacco as a whole.'' Another key area these findings may affect is the treatment of chronic disease, Cooke said. Angiogenesis is desirable, for example, in heart disease. Scientists have been looking at whether drugs can spur the growth of healthy new blood vessels to take over the job of diseased ones. Nicotine agents should be studied in this area, according to Cooke. But since nicotine may spur unwanted blood vessel growth, he added, this study also cautions against giving therapeutic nicotine in a way that would affect the whole body. Instead, Cooke said, he believes such treatment should be ``locally delivered.'' Nicotine is already being studied as a therapy for diseases such as Alzheimer's and Parkinson's because brain cells have nicotine receptors and research has suggested the drug might help these conditions.

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