If you're being treated for atherosclerosis, everything your doctor believes about your life-threatening disease is wrong.

New research from the University of Virginia School of Medicine found that basic beliefs about the formation and composition of the dangerous plaques that build up in arteries and cause heart attacks and strokes are mistaken.

The new discoveries, say researchers, will force scientists to reevaluate their approaches to developing treatments and ditch some of their basic assumptions of the world's No. 1 killer.

"The leading cause of death worldwide is complications of atherosclerosis, and the most common end-stage disease is when an atherosclerotic plaque ruptures. If this occurs in one of your large coronary arteries, it's a catastrophic event," said Gary K. Owens, PhD, of UVA's Robert M. Berne Cardiovascular Research Center. "Once a plaque ruptures, it can induce formation of a large clot that can block blood flow to the downstream regions. This is what causes most heart attacks. The clot can also dislodge and cause a stroke if it lodges in a blood vessel in the brain. As such, understanding what controls the stability of plaques is extremely important. "

Until now, doctors have believed that smooth muscle cells — the cells that help blood vessels contract and dilate — helped the body battle the formation of atherosclerotic plaque. They were thought to move from their normal location in the blood vessel wall into the developing atherosclerotic plaque and try to wall off the accumulating fats and other harmful components of plaque. The belief has been that the more smooth muscle cells there are in a wall, particularly in the innermost layer referred to as the "fibrous cap," the more stable the plaque is and the less danger of rupture.

The new research shows that, in fact, the cells don't form a barrier but contribute to the plaque itself. Some researchers had suspected that they failed to identify a small number of smooth muscle cells in advanced atherosclerotic lesions, but they discovered that the true number was very high — 82 percent.

"We have grossly underestimated how many smooth muscle cells are in the lesion," Owens said.

Now, the role of smooth muscle cells appears very complicated. Are they good or bad? Should treatments try to encourage more? It's no longer simple, and the problem is made all the more complicated by the fact that some smooth muscle cells were misidentified as immune cells called macrophages, while some macrophage-derived cells were disguised as smooth muscle cells.

Even scientists are confused and, according to Owens, this has led to "complete ambiguity as to which cell is which within the lesion."

In their ground-breaking study, the researchers genetically tagged young smooth muscle cells in mice and watched to see how atherosclerotic plaque developed over time, tracking the cells and their successors. They found that many more smooth muscles cells than previously thought were inside the plaque itself.

The team also found that when a gene called Klf4, which plays a role in smooth muscle cell changes inside the lesions, was deactivated, atherosclerotic plaques shrank "dramatically." This finding may lead to developing therapies to control the smooth muscles within lesions to treat atherosclerosis.

Study results were published in the journal Nature Medicine.