Heart Disease Research Focuses on Role of the Immune System

The immune system and the inflammation it produces protect us. However, if left unchecked, these same guardians can prove harmful.

An EVMS team of researchers led by scientist Elena V. Galkina, PhD, assistant professor of microbiology and molecular cell biology, has received a $1.7 million grant from the National Institutes of Health (NIH) to study atherosclerosis, a disease where the immune response can be detrimental. Their work may help identify new ways to battle heart disease.

Dr. Galkina and her colleagues know that atherosclerosis, the major pathological process that leads to heart attacks, is linked to an immune response against components of lipoproteins and the arterial wall.  Dr. Galkina’s research is focusing on how subsets of T lymphocytes, namely T helper 17 (Th17) cells and T regulatory (Treg) cells, impact inflammation in blood vessels during the early stages of the disease.

While Th17 cells may trigger the immune response, Tregs are responsible for reining in the immune system and preventing further damage to the artery.

“When plaque builds in the vessels, the body instigates an immune response, which causes inflammation,” explains Dr. Galkina. Unfortunately, this process is not very well controlled by the immune system and results in chronic long-term inflammation that harms the vessel wall.

Dr. Galkina and her team found inconsistencies in the levels of the immune cells in rodents and in tissue samples donated by coronary artery disease patients treated at Sentara Norfolk General’s Heart Hospital.

“In atherosclerotic rodents and coronary artery disease patients, we noticed elevated levels of Th17 cells but low levels of Treg cells, so we decided to look at the role of these particular cells in atherosclerosis,” says Matthew J. Butcher, a PhD candidate and member of Dr. Galkina’s laboratory.

“We know that Tregs are critical to dampening inflammation and we know that this balance gets tipped toward the inflammatory side in atherosclerosis,” says Dr. Galkina. “What we need to determine is what mechanism tips the scale in one direction or another. We also need to see if they reciprocally regulate each other.”

"Basically," Dr. Galkina says, "a pro-inflammatory environment is like a brush fire and inflammatory environment is like a brush fire and Tregs are like water. If there are plenty of Tregs in the artery, they would quickly squelch the immune response. However, if there aren’t enough Tregs present in the artery, it would be akin to trying to douse an inferno with a squirt gun.”

According to the Centers for Disease Control and Prevention, nearly 785,000 Americans had a heart attack last year. In addition, according to the most recent American Heart Association report, 16.3 million Americans currently have coronary heart disease and 7.9 million Americans have had a heart attack in the past.

In addition to better understanding the role of different T cell subsets and their reciprocal regulation in the immune response during atherosclerosis, Dr. Galkina hopes her research will facilitate new approaches toward the prevention and treatment of disease.