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Nicotine Can Boost Blood Vessel Growth

But its potential as helpful drug doesn't make smoking any better for you, experts say

FRIDAY, Dec. 15, 2006 (HealthDay News) -- Nicotine may not be all bad: A study found it stimulated new blood vessel growth in mice by actively signaling their bone marrow to release vessel-forming adult stem cells.

The finding might translate to the use someday of nicotine as a means of helping wound healing and other conditions where new blood vessel growth is key, experts say. It also gives insight into unwanted vessel growth, such as that which happens during tumor formation.

The findings don't mean doctors will ever recommend smoking, however.

"I don't want people to think that smoking is good for you," cautioned co-author Dr. John P. Cooke, a professor of medicine at Stanford University's School of Medicine in California. "Tobacco smoke contains 4,000 compounds, and nicotine is just one of them. And what we've discovered is that nicotine alone can cause blood vessel growth."

"Blood vessel growth is like fire," Cooke added. "It's neither good nor bad. So, certainly nicotine-associated blood vessel formation can cause problems, in the context of enhancing tumor growth, causing macular degeneration and blindness, or promoting coronary plaque. But, on the other hand, knowing that this phenomenon occurs, we can potentially manipulate it in a way that can be therapeutic -- such as to enhance insufficient wound healing where part of the problem is related to poor blood vessel growth."

The findings, based on animal and test-tube research, are reported in the Dec. 19 issue of the Journal of the American College of Cardiology.

Cooke's team's prior research had already demonstrated nicotine's ability to promote blood vessel growth, known as the "angiogenic effect." In this new study, they set out to uncover the mechanism driving this process.

The researchers first took several pairs of 10-week old male and female mice and surgically sewed them together -- male to female -- at their flanks. The suturing provoked the development of a shared circulatory system.

About four weeks after this procedure was performed, the authors surgically instigated a blood vessel blockage in the hind limb of the female mouse.

The purpose was to test the notion that a dose of nicotine might induce new blood vessels to grow around the blockage by triggering the mice's bone marrow to release adult stem cells. These cells, called EPCs, are released from marrow into the bloodstream, where they migrate to the site of injury.

The only way to tell that the blood-forming cells were coming from bone marrow and not arising at the site of injury (on the female's flank) was to track markers specific to the male mouse's cells, the researchers explained.

But would nicotine speed this angiogenic process? To test the theory, the researchers exposed some of the mouse pairs to a daily oral dose of nicotine mixed with saccharine and water soon after surgery. The other mouse pairs received a localized injection of nicotine directly into the limb with the blockage.

Over the course of a two-week nicotine diet, Cooke's team tracked the progress of bone marrow cell production and circulation in the paired mice.

Nicotine treatment was associated with a boost in the number of EPC stem cells in both the bone marrow and spleen of the conjoined mice, the researchers report. This was backed up by further lab tests.

In addition, some of the new blood vessels that formed around the hind limb blockage during nicotine treatment were made up of those EPC cells originating in the marrow, the team said.

Cooke and his colleagues also found that the oral dose of nicotine had a stronger effect on blood vessel growth than the local injection. The oral dose provoked a 76 percent increase in capillary density at the site of the blockage vs. a 45 percent increase from targeted injections.

Not all the blood vessel growth was attributable to EPC cells mobilized into action by nicotine, Cooke's team stressed, and the exact mechanism driving nicotine's angiogenic effect remains unclear.

Nevertheless, the finding suggest that nicotine-based agents may have a role to play in boosting blood vessel formation in patients who need it.

All of this is separate from nicotine's dangerously addictive properties in tobacco products, however.

"We know nicotine is bad," agreed Dr. Byron K. Lee, an assistant professor of cardiology at the University of California, San Francisco. "The way most of society consumes it can cause heart attacks and cancer and leads to other vascular diseases like stroke."

"But there could be a situation where you could release nicotine to have some beneficial effects," he noted, "for example, in a small part of the body where there's blockage of the arteries that feed the heart. Because we know that, over time, the body develops new blood vessels that relieve the pain. But that process takes months to years to form. So, if we could somehow use nicotine to get those areas to spring new blood vessels faster, we could help people."

"We're not there yet," Lee added. "None of the studies have fully panned out yet. But we should try to see whether or not nicotine works, and if it happens to work, then it could be potentially fantastic."

More information

For more on nicotine, visit the American Heart Association.

SOURCES: John P. Cooke , M.D., Ph.D., professor, medicine, Stanford University School of Medicine, Stanford, Calif.; Byron K. Lee, M.D., assistant professor, cardiology, University of California, San Francisco; Dec. 19, 2006, Journal of the American College of Cardiology
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