not known which genes might control the pigeons' heart vessel tissue-building process, so Wagner's group focused on "transcription factors," which regulate whether a gene is expressed and at what rate. The group's aim was to see if certain transcription factors might be found in altered amounts in the smooth muscle cells of pigeons that are prone to atherosclerosis.

They screened 54 different transcription factors and found that one, known as STAT4, was 10 times higher in the white carneau pigeons with genetic heart disease. Further testing showed that stimulating STAT4 in smooth muscle cells in the laboratory resulted in a threefold increase in cell growth.

"We were very surprised," said Wagner. "This is one of the first reports of this factor being found in smooth muscle cells."

Wagner said the finding has potential for helping scientists solve the problem of restenosis.

"Interfering with these factors and the signaling pathways involving STAT4 may be potentially important in atherosclerosis therapy," he said. "We may identify ways to reduce or block its effect and slow or stop the unwanted growth of cells."

He said that by finding the transcription factor, researchers can concentrate on modifying its pathway, and won't need to know which or how many genes it affects.

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Contact: Karen Richardson
krchrdsn@wfubmc.edu
336-716-4453
Wake Forest University Baptist Medical Center
28-Jul-2006

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