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Smooth muscle cells provide CV clues

Li.jpg (29833 bytes) Dr. Li is studying the molecular mechanisms of cardiovascular disease.

"Cardiovascular disease is still the number one killer in the United States," said Li Li, PhD, assistant professor of internal medicine. "We have ways to help people live longer with it, but there are still many questions about the molecular workings." With that in mind, Dr. Li is conducting research to learn more about the molecular mechanisms for the pathogenesis of this disease. Specifically, she is characterizing regulation of SM22, a gene that is highly expressed in smooth muscle cells.

What makes SM22 regulation unique is that its expression in different smooth muscles is regulated by different control elements. Although smooth muscle is contained in veins and arteries, the control region identified for SM22 expression, called the SM22 promoter, is only active in the arteries. The reason for this isolated activation is currently under investigation by Dr. Li with more than $1.4 million in support over the next five years. This is her first National Institutes of Health grant, although she has been conducting cellular and molecular cardiology research at the WSU School of Medicine since 1996. She is also funded by the American Heart Association.

"We are trying to understand why the SM22 promoter is active only in the arterial vasculature, but not in visceral or venous areas," said Dr. Li. "This is important because abnormalities in smooth muscle cells have been associated with cardiovascular disease. At this point, little is known about the mechanisms that control the proliferation and differentiation of those cells during cardiovascular development."

Studies with transgenic mice suggest that serum responsive factor (SRF) may play an important role in SM22 gene regulation. SRF is a CArG box binding protein that may be directly involved in the promoter activation in the arterial smooth muscle cells.

From a more clinical standpoint, this research has immediate application for understanding how to deal with cardiovascular disease. Because the SM22 promoter is the first control region identified to direct gene expression in arterial smooth muscle, it offers a valuable tool to deliver therapeutic genes into diseased arteries in gene therapy.

Dr. Li’s current research will also have the potential to control cardiovascular diseases. For example, vein grafting is commonly performed so that a vein can be taken from the leg and moved to the chest for a heart bypass. In many cases, the veins eventually arterialize and lead to vessel narrowing. This physiological change necessitates a new bypass. Dr. Li’s research may provide insight about the molecular development of veins and arteries that causes this to happen.

"A better understanding of these mechanisms could provide the basis for gene therapies to treat or correct cardiovascular disease in the future," Dr. Li said.

Science_cover.jpg (24767 bytes) This image produced by Dr. Li which was featured on the cover of Science in 1996 illustrates the arterial vasculature development, which is under investigation in Dr. Li’s lab.

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