Heart vessel clogs linked to p53.

For years, researchers have gathered evidence implicating herpesviruses not only in fever blisters, flu symptoms, and genital sores, but also in coronary artery disease (SN: 4/3/93, p.216). In addition, scientists searching for causes of cancer have tied defects in the tumor suppressor gene p53 to the uncontrolled cell growth that leads to tumors (SN: 11/27/93, p.356).

Now, the paths of those seemingly unrelated investigations have crossed.

Cytomegalovirus, a member of the herpes family, makes a protein that appears to disable the p53 protein. As a result, smooth muscle cells in blood vessels can proliferate until they impede blood flow, explains Edith H. Speir, a cell biologist at the National Heart, Lung, and Blood Institute in Bethesda, Md.

She and her colleagues studied why 25 to 50 percent of people who undergo angioplasty--a procedure in which cardiologists insert and inflate a small balloon to unclog heart vessels--return within 6 months, their vessels clogged again. Unlike the initial blockages, which consist of a complex mixture of fatlike substances, debris from blood, and few intact cells, the new ones consist primarily of smooth muscle cells, which may overreact as they repair damage from the angioplasty, Speir explains.

Cardiologists often treat secondary blockages, called coronary restenosis, by removing the clogging clump of cells. Speir's team examined 60 such clumps; they detected p53 in 23 of them. In contrast, they did not find p53 in 20 samples taken from people treated for the first time.

Contrary to what the researchers expected, the p53 genes were perfectly normal, she adds. But almost 80 percent of the clumps with p53 also contained cytomegalovirus. When the researchers later infected smooth muscle cells with this virus, p53 increased in parallel with a viral protein known to stimulate DNA replication, they report in the July 15 SCIENCE. That viral protein may block p53 activity.

Such a link could be expected, says collaborator Eng-Shang Huang of the University of North Carolina at Chapel Hill. "But it will be a surprise to a whole bunch of clinicians," he predicts, adding that this virus may be key in many diseases, including cancer.