Scientists have uncovered details of a phenomenon that contributes to coronary artery disease, more commonly known as heart disease, an advance that may lead to new drug treatments for fighting heart disease, according to a study.

Soon after cholesterol and fat start depositing on the lining of the blood vessels that supply your heart, the smooth muscle cells that give the blood vessels strength and flexibility start to get bigger and multiply.

While scientists studying the phenomenon suspect these vascular smooth muscle cells are trying to help, this atypical behaviour for these strong cells instead contributes to coronary artery disease.

In a bit of a vicious cycle, stents as well as bypass grafts used to treat coronary artery disease can prompt the same response.

Now Medical College of Georgia (MCG) scientists report new insight into how the cells enable this unhealthy growth and a new target to intervene.

The endothelial cells that line our blood vessels are in constant communication with the layers of vascular smooth muscle cells that encase them and play a key role in regulating our blood pressure, said Yuqing Huo, director of the Vascular Inflammation Program in the Vascular Biology Center at MCG.

In states of good health, for example, the two cell types share messages about how it is time for our blood vessels to dilate a little because we are exercising. Early in vascular disease, however, the conversations change, said Huo, corresponding author of the study in the journal Circulation.

"They get the message that something is wrong," said Huo, and existing cells get exponentially bigger and start proliferating, which these cells don't normally do, perhaps in an effort to make more room inside for blood to flow since cholesterol and fat are narrowing the existing passageway.

"Normally, the smooth muscle cells provide strength. If they start to proliferate a lot, it changes their identity," Huo says.

Whatever the reason, the result is more narrowing and scarring of the vital passageway for blood and worsening disease. So, the scientists looked at the building blocks needed to enable the unhealthy response.

They knew that growing more and bigger cells required more DNA, RNA and the proteins they produce. To make that happen required more purines, one of two chemical compounds in the body used to make the building blocks of DNA, in this case, adenine and guanine.

What they didn't know was precisely how these cells make more purine when faced with arterial disease, says Dr Qian Ma, a postdoctoral fellow with Huo and the study's first author.

There are two fundamental ways cells come up with purine: One is to essentially make it from scratch, called de novo purine synthesis, and the other is through recycling.

The MCG scientists are the first to find that the higher-energy consuming de novo purine synthesis is increased in this scenario, Ma said. In the scar tissue and plaque inside blood vessels of an experimental model and humans, Huo, Ma and their colleagues also found increased expression of ATIC, a gene essential to purine production.

When they knocked ATIC out body wide as well as specifically in the vascular smooth muscle cells, it inhibited purine production, which decreased the production of DNA and RNA, and the subsequent proliferation of the smooth muscle cells.

The net effect of less ATIC was reduced formation of scar tissue in experimental models of both atherosclerosis and restenosis, or re-narrowing of blood vessels, including buildup inside the stents themselves, that can occur after procedures like angioplasty to open clogged vessels and placement of stents to help keep them open.

"It takes away one of the building blocks of DNA," says Ma. "The blood vessels remained normal. The lumen stayed open." The response shows that the production of purine plays a key role in the proliferation of smooth muscle cells and pegs ATIC as a logical point to intervene, the scientists say.

“Our model demonstrates that this ATIC is important and targetable,” says Ma.