Dysregulated immune cells may drive silent inflammation after a heart attack

Coronary artery disease, which is caused by plaque buildup in the arteries that supply blood to the heart, can appear stable for long periods without causing any symptoms. But the disease can become unstable at any time and cause a heart attack. Following a heart attack, low-grade inflammation can persist in the body for several months or even years. A large body of research suggests that this prolonged inflammation increases the risk of another heart attack. More than 20,000 people in Sweden suffer a heart attack every year.

"Treatment following a heart attack has developed tremendously, with medicines and balloon angioplasty, but we still don't understand well enough the inflammation that persists in these patients," says Lena Jonasson, professor of cardiology at Linköping University and consultant at Linköping University Hospital, who led the study published in the journalArteriosclerosis, Thrombosis and Vascular Biology.

Neutrophils drew closer scrutiny

The Linköping researchers were particularly interested in a type of white blood cell known as neutrophils. They are the body's most abundant immune cells and need to respond quickly to kill bacteria and damaged cells.

"In previous studies, however, we showed that neutrophils in patients with stable coronary artery disease are too easily activated. When exposed to stress, they respond more strongly than neutrophils from healthy individuals. They are also present in greater numbers in patients," Jonasson says.

Although neutrophils are abundant, they circulate in the bloodstream for only 24 hours. They are then programmed to die. This tight regulation of neutrophils is considered crucial for ensuring that an inflammatory reaction subsides once it is no longer needed. The LiU researchers suspected that something might be wrong with the way neutrophils behave in coronary artery disease.

Testing cells from patients and controls

To investigate this, they isolated neutrophils from the blood of 20 patients who had experienced a heart attack and 19 healthy individuals of the same sex and age. The patients' coronary artery disease was optimally treated in accordance with current guidelines, and they had no symptoms of their disease. Nor did any of them show signs of inflammation according to the routine C-reactive protein (CRP) test.

In a series of experiments, the researchers measured how neutrophils from patients and healthy individuals responded. They also investigated what happened when the neutrophils were mixed with another type of immune cell from the same person, known as regulatory T cells. As their name suggests, these cells regulate the activity of other immune cells and suppress inflammation. One way they do this is by helping neutrophils to die—if everything is functioning as it should.

Cells that fail to switch off

"We showed that neutrophils in patients with stable coronary artery disease do not die as they should. They persist and remain highly active. We also found that regulatory T cells did not kill the patients' neutrophils, unlike those from healthy individuals," says Maike Schneider, doctoral student at Linköping University and first author of the paper.

The findings show that dysregulated neutrophils may play a key role in the persistent low-grade inflammation seen in chronic coronary syndrome.

"At present, only CRP is recommended for measuring inflammation in coronary artery disease, but a low CRP level tells us very little. We need to become better at diagnosing low-grade inflammation in patients and understanding the biological mechanisms, so that we can provide the right treatment and develop new medicines," Schneider says.

This article was originally published on MedicalXpress Breaking News-and-Events.