Stanford Report, July 11, 2001

Researchers discover nicotine stimulates growth of new blood vessels

BY KRISTA CONGER

Researchers speculate that when nicotine binds to the receptor on endothelial cells it stimulates the cells to release a cascade of chemicals that promote the formation of new blood vessels. The new vessels then deliver oxygen and nutrients to the interior of tumors and plaque deposits.

The Stanford researchers were surprised to find how strongly nicotine stimulates new blood vessel growth, a process known as angiogenesis.

"We expected to see that nicotine impairs angiogenesis because it's known that smoking impairs endothelial function," said Chris Heeschen, the first author of the paper and a postdoctoral fellow in cardiovascular medicine in Cooke's laboratory. "But nicotine is not smoking."

Under some experimental conditions the magnitude of nicotine's effect was comparable to that seen with naturally occurring proteins involved in angiogenesis. In every case, chemicals known to inhibit other molecules associated with angiogenesis also blocked the effect of nicotine -- confirming that nicotine affects blood vessel formation.

The researchers began the study by testing whether nicotine could stimulate the division of cultured endothelial cells. They found that nicotine was as effective as vascular endothelial growth factor, or VEGF -- a naturally occurring, well-defined protein that has long been known to enhance endothelial cell proliferation. Cells cultured in the presence of nicotine or VEGF also assembled themselves into whorls in the tissue culture dish -- perhaps a preliminary step to forming new blood vessels. Chemicals that block nicotine's binding to the receptor also blocked proliferation of the cells.

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