Protein linked to immune attack may stop sudden death after heart attacks

Scientists at Mass General Brigham discovered that an immune protein, Resistin-like molecule gamma, damages heart cells after heart attacks, triggering deadly rhythms. Blocking it could dramatically reduce sudden cardiac death risk.

After a heart attack, the body’s immune system rushes to repair damaged tissue. But new research from Massachusetts General Hospital (MGH) shows that this same defense response can backfire—with fatal consequences.

A team led by Dr. Nina Kumowski and Dr. Matthias Nahrendorf discovered that an immune protein called Resistin-like molecule gamma (RELMγ) literally punches holes in heart cells, triggering dangerous electrical disturbances that can cause sudden cardiac death.

Their study, published in Science, reveals how blocking this single protein reduced deadly arrhythmias by twelvefold in mice, offering a potential new path to preventing sudden death after heart attacks.

When the body turns against the heart

Heart attacks, or myocardial infarctions, occur when blood flow to part of the heart is blocked, starving cells of oxygen. This damage can spark erratic heart rhythms known as ventricular tachycardia or ventricular fibrillation, which often cause death within minutes.

Until now, scientists believed these dangerous rhythms stemmed only from electrical instability in heart cells. But the MGH team found that immune cells called neutrophils, which flood the injured area within hours of a heart attack, also play a key role in disrupting heart function.

Using genetic and imaging tools, the researchers showed that neutrophils produce high levels of RELMγ, a protein that binds to and damages heart cell membranes. “We found that this immune molecule quite literally punches holes into heart cells,” said Dr. Kumowski. “That triggers rapid, irregular rhythms that can be fatal.”

Turning off the killer protein

To test whether this molecule directly drives sudden cardiac death, the team engineered mice whose neutrophils lacked the gene for RELMγ. The results were striking—these mice were 12 times less likely to develop life-threatening arrhythmias after a heart attack.

The researchers also found a similar human version of the protein, called Resistin (RETN), elevated in damaged heart tissue from patients. This suggests the same mechanism may be at play in people.

A new frontier for treatment

Today’s heart attack treatments focus mainly on restoring blood flow, but these findings suggest that targeting the immune response could be equally vital.

“We’ve long known that inflammation worsens heart damage after a heart attack,” said Dr. Nahrendorf. “What we didn’t know is that immune cells could directly cause arrhythmias. Blocking these molecules could save lives.”

The next step for the team is to develop therapies that neutralize RELMγ and test whether this reduces arrhythmias and tissue damage—not just in mice, but eventually in humans.

Why it matters

Sudden cardiac death remains one of the leading causes of mortality worldwide, often striking patients who seemed to be recovering after a heart attack. If further research confirms these findings, a simple treatment that blocks this rogue immune protein could transform post-heart attack care.

“This work shows the immune system can be both a healer and a destroyer,” said Dr. Kumowski. “By understanding how it turns harmful, we can finally learn to protect the heart when it’s most vulnerable.”