(RxWiki News) Researchers have known for a while that chronic inflammation may play a part in coronary artery disease, but haven’t known where the inflammation may be coming from — until now.
A new study found that people with coronary artery disease may have hyper-aggressive immune cells that are lodged in arterial plaque, binging on glucose. The presence of these immune cells may put the heart in a hyper-inflammatory state.
The authors of this study said that if they could stop glucose over consumption, they may be able to prevent this hyper-inflammatory state.
Coronary artery disease is a broad term for disease or damage in major blood vessels in the heart, often entailing plaque buildup in the arteries, which impedes blood flow, often causing a heart attack.
Though lipids (fats, waxes and sterols) are the main part of arterial plaque, plaque also contains a type of immune cell called macrophages. Macrophages fall into two categories — M2 macrophages that stimulate blood flow, repair tissue damage and eat debris, and M1 macrophages that find pathogens and aggressively call other immune cells to the scene.
M1 macrophages attack invaders by releasing biohazardous chemicals called free radicals, which are linked to inflammation. They also release proteins to ramp up the entire immune system to high-alert mode.
"Some believe that coronary artery disease patients' macrophages are so preoccupied with their inflammatory power trip they neglect their clean-up tasks," said senior study author Cornelia Weyand, MD, a professor and chief of immunology and rheumatology at Stanford University Medical Center, in a press release.
Chronic inflammation can make plaque brittle, making it more likely to break off and cause a clot.
To conduct this study, Dr. Weyand and her team looked at monocytes (what M1 and M2 macrophages start out as) from 140 people with coronary artery disease who had had at least one heart attack. They compared them with monocytes from 105 healthy participants.
Within the coronary artery disease group, the monocytes were more likely to develop into the aggressive M1 macrophages that produce the proteins that put the immune system on high alert, these researchers found.
"Even before taking up residence in arterial plaque and becoming full-fledged macrophages, these patients' monocytes were already leaning toward becoming inflammatory," Dr. Weyand said.
The research team also found that the macrophages in the coronary artery disease group had double the number of free radicals (biohazardous chemicals), compared to those of the healthy group. The macrophages of the coronary artery disease group took up glucose (sugar) at a higher rate than normal cells did, which may cause them to break down and overheat, producing free radicals.
Researchers found that the high levels of free radicals were triggering an enzyme called PKM2 to abandon its regular job — generating energy from glucose — to instead trigger more proteins to put the immune system on high alert.
The good news is that interventions like blocking glucose, soaking up free radicals and stopping PKM2’s status change may reduce inflammation, Dr. Weyand said. She said this discovery could lead to new therapeutic approaches.
This study was published Feb. 29 in The Journal of Experimental Medicine. It was funded by the National Institutes of Health, the Govenar Discovery Fund and Stanford's Department of Medicine. The authors declared no conflicts of interest.