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University of Virginia researchers identify genes responsible for coronary artery disease

Coronary artery disease is the No. 1 cause of death worldwide.

CHARLOTTESVILLE, Va. — Coronary artery disease is the most common form of heart disease, affecting more than 20 million Americans. It’s estimated to be responsible for 1 in 4 deaths in the United States each year. Now, new findings by University of Virginia researchers will advance efforts to develop better treatments.

Researchers have identified genes that play key roles in the development of coronary artery disease. UVA’s findings essentially pick culprits responsible for the disease out of a far, far larger lineup of potential genetic suspects. 

“Genetic studies done in more than 1 million people in the last 15 years identified hundreds of locations on our chromosomes that increase the risk of having a heart attack,” said senior researcher Mete Civelek, PhD, of UVA’s Center for Public Health Genomics and the Department of Biomedical Engineering, a joint program of the School of Medicine and School of Engineering. “We now identified the genes that are responsible for this risk at these locations. We will be able to use these findings as new therapeutic targets.”

CAD is caused by the buildup of fatty plaques in the walls of the arteries that supply blood to the heart, but the genetic (inherited) factors that contribute to its development remain murky.

To home in on genes important in the development of CAD, Civelek and his team examined cells collected from 151 previously healthy heart transplant donors from a variety of racial and ethnic backgrounds. This provided the scientists with a tremendous amount of information on gene activity in smooth muscle cells. These cells naturally line our arteries, but they also can serve as the foundation for the fatty plaques that build up inside those arteries.

Using the gene-activity data, the scientists worked backward to triangulate specific gene variations responsible for harmful changes in the smooth muscle cells. Understanding these changes sheds light on plaque formation, a process called atherosclerosis, and, ultimately, on the molecular mechanisms responsible for coronary artery disease. 

“Current drugs that doctors prescribe work to reduce risk factors for heart disease, such as cholesterol-lowering drugs,” Civelek said in a press statement. “However, we need to identify drugs that target the disease where it develops. That is why it is important to find the genes responsible for the disease development in the arteries, because that is where the plaques form.”

The researchers have published their findings in the scientific journal Circulation Research.

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