A team of US researchers and their collaborators have identified genes that play key roles in the development of coronary artery disease, the top cause of death worldwide.
The University of Virginia (UVA) researchers’ findings essentially pick culprits responsible for coronary artery disease (CAD) out of a far, far larger lineup of potential genetic suspects, giving scientists promising targets as they work to develop new and better treatments.
“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, UVA’s Center for Public Health Genomics and the Department of Biomedical 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,” Civelek added in a paper published in Circulation Research journal.
Coronary artery disease 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 decode this, Civelek and his team examined cells collected from 151 previously healthy heart transplant donors from a variety of racial and ethnic backgrounds.
Using the gene-activity data, the scientists worked backward to triangulate specific gene variations responsible for harmful changes in the smooth muscle cells.
Current drugs that doctors prescribe work to reduce risk factors for heart disease, such as cholesterol-lowering drugs.
“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,” said Civelek.
The new research provides many important insights into coronary artery disease. For example, the researchers found notable differences in gene activity between males and females in smooth muscle cells.
They also identified important differences in smooth muscle cells that were multiplying, or “proliferating,” and those that were not.
“We expect that our findings will provide a rich catalog of genes for the cardiovascular community to study in years to come,” Civelek said.
