Newly Discovered Gene Appears to Have Atheroprotective Effect

Researchers at the University of Virginia have shed light on how our genes affect our risk for coronary artery disease. In addition to identifying gene variants that influence risk, they found that one gene in particular appears to have a protective effect. Their study was published in Circulation Research.

"Current drugs for coronary artery disease treat the risk factors, such as cholesterol or hypertension," said lead researcher Mete Civelek. "Our studies used a genetic approach to identify the mechanisms in the wall of the blood vessels where the disease actually develops."

To better understand the risk factors associated with coronary artery disease, Civelek and his colleagues began by examining cells from 151 ethnically diverse heart donors. These cells, called vascular smooth muscle cells, can prove either beneficial or harmful in the buildup of fatty plaques inside our blood vessels. That buildup, known as atherosclerosis, causes coronary artery disease.

The researchers examined the smooth muscle cells for 12 different characteristics that influence the stability of the plaque patches. The researchers then compared their findings with vast amounts of genetic data to determine how genes were affecting the smooth muscle cells. They found that naturally occurring gene variations have significant influence on the functions of these cells that lead to atherosclerosis and CAD. These variants, they found, affect how smooth muscle cells behave—how they proliferate, migrate and calcify. These factors determine the stability of the protective caps atop the plaque lesions.

"We found that nearly half of the gene variants that increase the risk for coronary artery disease also affect how the smooth muscle cells behave," said researcher Rédouane Aherrahrou. "This implies that we should study these cells in more detail when it comes to understanding the inherited risk for coronary artery disease." Civelek's team also identified a gene, MIA3, that appears very important in ensuring thick, stable protective caps—the desirable kind.