Smooth muscle cells may hold key

USA Today (Society for the Advancement of Education), Oct, 2005

A basic mechanism by which smooth muscle cells that line blood vessels can grow--sometimes abnormally--has been discovered by researchers at the University of Texas Southwestern Medical Center, Dallas, suggesting methods of treatment for a number of coronary diseases. Abnormal growth of cells inside blood vessels is involved in hypertension, coronary artery disease, tumors called leiosarcomas, and various other conditions.

"By understanding this detailed mechanism, it is now possible to begin to design therapies to interfere with it and thereby potentially prevent various vascular disorders in humans," maintains Eric Olson, chairman of Molecular Biology.

There are three types of muscles in the body--skeletal, cardiac, and smooth. Smooth cells make up the stomach, intestine, blood vessels, and other organs. Unlike the skeletal and cardiac muscles, smooth muscle cells either can rest in their final form, which allows vessels to contract, or can divide into new cells.

Researchers have known about several signals that can stop smooth muscle cells from dividing and enable them to contract, but little is understood about how this cascade of interactions works. The protein myocardin, discovered in Olson's lab in 2003, is known to bind to DNA and stimulate the expression of genes that control muscle contraction. How myocardin is regulated, however, has been a mystery.

Olson and fellow researchers focused on a molecule called Foxo4, to see whether it might control myocardin; they found that it turns off myocardin, thus allowing smooth muscle cells to stop contracting and grow. The level of Foxo4, in turn, increases or decreases depending on what kind of signals the smooth muscle receives. This complexity suggests many pathways for future treatments. For instance, a treatment might directly control the level of Foxo4, or it may involve one of the signals that regulate it.

"Now that we understand the nuts and bolts of this problem, we can use that information to find ways of disrupting the disease process," Olson says. "We have several ideas in this regard, which we intend to test."