Growth factors boost heart's blood flow.

Genetically engineered growth factors can improve the heart's blood supply in dogs and pigs, researchers say. They believe such drugs may one day provide humans with a treatment to counter clogged coronary arteries, the main vessels that supply the heart with blood.

People with disease-narrowed coronary arteries experience repeated bouts of myocardial ischemia, a dangerous decline in the volume of blood flowing to heart muscle. Cardiologists know that everyone has so-called collateral vessels that bring small amounts of blood to the heart. These collateral vessels enlarge when the coronary arteries are blocked, thus bypassing the obstruction. In most cases, however, collateral circulation can't make up the shortfall in blood volume, so patients may still experience crushing chest pain.

National Heart, Lung, and Blood Institute researchers Stephen E. Epstein and Ellis E Unger wanted to find out if they could improve upon nature's own method of providing alternate routes for the heart's blood supply. They focused on two growth factors, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Both are short proteins thought to play a role in the body's normal production of new blood vessels.

In one investigation, the researchers relied on dogs and a device that gradually narrows the left coronary artery. That experimental process mimics what happens to humans when the coronary arteries become choked with fatty plaque, Epstein says. Next, the team injected VEGF, FGF, or an inactive placebo directly into the arteries of the dogs in the study. After four weeks, each growth factor boosted collateral circulation by an average of 40 percent, Epstein said last week at the American Heart Association's annual science writers' seminar, held in Clearwater Beach, Fla.

The duo also wanted to see if a very short course of growth factor could spark more collateral blood flow. They repeated their experiment with dogs but this time gave just FGF for a period of seven days. Even brief treatment with FGF provoked a substantial increase in collateral blood flow.

If people with coronary artery disease obtained. such a boost in their collateral circulation, they might avoid the sometimes painful ischemic episodes, which can leave regions of the heart with dead or damaged tissue, Epstein says. More important, such treatment might help patients avoid angioplasty or bypass surgery, comments Michael Simons of Beth Israel Hospital in Boston, whose research with pigs also shows FGF helps boost collateral blood supply.

Are such growth factors sale? Nobody really knows. Scientists believe that growth factors encourage the proliferation of smooth muscle cells that help make up artery walls. Epstein wonders whether such treatment could actually narrow the already diseased arteries even further. To test that worrisome possibility, Epstein and Unger injured the leg arteries of dogs and exposed those vessels to FGE The growth factor triggered no abnormal growth of artery cells -- at least in this preliminary experiment. "So far. we're encouraged," Epstein says.

Another concern revolves around the speculation that growth factors could rev up indolent tumors. Many people harbor such tumors, which may not cause problems for years, Epstein points out. Yet long-term exposure to growth factors might help transform slow-growing tumors into aggressive cancers.

Simons doesn't believe cancer is a likely side effect, especially if treatment is brief. His group plans a safety trial of growth factors given to humans with severe coronary artery disease.