Circulation: First-responder cells after heart attack promote accelerated inflammation

Columbus, Ohio — A new study in mice shows that after a heart attack, first responder cells that initiate repair work so frantically to repair damage that they trigger more than necessary.

Based on these findings, scientists are seeking interventions to make the recovery process after a heart attack more balanced

In a series of studies, researchers have identified those cellular events that lead to the need for reinforcements—a wave of additional first responders—to arrive at the repair site

The first responder cells are neutrophils, the most abundant of all white blood cells, whose role is to heal wounds and clear infections

"We're just trying to prevent further damage to the heart by reducing the neutrophil response," said Prabhakara Nagareddy, associate professor of cardiac surgery at the Ohio State University College of Medicine.

"We set out to study the role of inflammation in scarring to see if we might be able to change that process

The latest research on this work is published in the journal Circulation on January 4, 2022

During a heart attack, the loss of nutrients and oxygen can lead to the death of heart muscle cells (cardiomyocytes) and other cells, and ultimately scarring at the site of loss

"When you're injured, the body heals

In these studies, the researchers induced heart attack symptoms in mice and used the models to see how inflammation starts and increases during heart repair

Neutrophils are undoubtedly a key part of the problem

However, because neutrophils are critical in all wound healing and fighting infection, their first-response role in cardiac repair cannot be directly eliminated

As part of the investigation, the researchers found that the first wave of neutrophils that reach the damaged heart perceives the damage as so severe that they sacrifice themselves to prevent further damage, releasing their entire contents -- including cells called alarmins protein

Insinuates neutrophils and then does something unexpected: They migrate backwards from the heart to the bone marrow and release pro-inflammatory proteins, which prompts bone marrow stem cells to make more neutrophils, all processes, so that inflammation ceases Need to repair the heart

In a recent paper, experiments in mice using genetic techniques or drugs revealed at least two potential targets for intervention: restricting reverse migration of neutrophils that have already been initiated, or inhibiting neutrophils in the bone marrow release pro-inflammatory proteins

"Neutrophils don't see distinctions between tissues, so we need to focus on signaling pathways or mechanisms when neutrophils are busy and find the right time to intervene," Nagareddy said

This work was supported by grants from the National Institutes of Health and start-up grants from Ohio State
.