Heart attacks leave behind a wound that the body must scar over to survive, yet too much scar tissue slowly strangles the heart's ability to pump, and medicine has long lacked a way to address that excess. In a mouse study from University of Utah Health, published in Nature Communications, researchers found that quieting a single protein, AEBP1, in the cells that manufacture scar tissue kept heart failure from taking hold. The finding offers a glimpse of prevention rather than cure, a reminder that healing and harm can be made of the same material, and that timing may decide which one wins.
Blocking Protein AEBP1 Curbs Excess Heart Scarring and Prevents Heart Failure in Mice
Fibrosis is part of healing.
Mark
Why does this one protein matter so much?
Mimi
Because scarring in the heart currently has no treatment, and most heart failure is driven largely by it. AEBP1 triggers that scarring, so it's a concrete target.
Mark
What actually happened in the mice?
Mimi
They lowered AEBP1 in fibroblasts after a heart attack, and four weeks later heart function was significantly better.
Luke
Four weeks, in mice. That's what we can say. Nobody has shown this protects people over years.
Mark
And if the heart failure is already established?
Mimi
Then lowering AEBP1 did nothing. It seems to prevent bad scarring, not undo it.
Luke
That's a big caveat. Many patients meet doctors after damage is done.
Mark
Why not just block all scarring?
Mimi
Early scarring holds the heart together after a heart attack. Drakos put it simply: fibrosis is part of healing.
Luke
So the timing is unknown. The researchers say future studies must find the optimal moment.
Mark
Does the human evidence help?
Mimi
The gene is more active in advanced heart failure hearts, and in donated tissue, lowering AEBP1 reduced scarring.
Luke
That's tissue culture, though. It's suggestive, not proof that a drug would work in a patient.
Le Pouls
- After a heart attack, the body's repair crew of fibroblasts keeps laying down scar tissue long after it is needed, and the heart slowly stiffens.
- Heart failure caused by this excess scarring has no approved therapy, leaving clinicians with few tools to halt its advance.
- Researchers at University of Utah Health lowered AEBP1 in scar-producing cells and saw heart function significantly preserved in mice four weeks later.
- The protection disappeared once heart failure was already underway, so the approach can prevent scarring but has not been shown to reverse it.
- Human heart tissue hints that AEBP1 drives scarring in people too, but safety, timing, and effectiveness in patients remain untested.
Heart attacks leave behind a wound that the body must scar over to survive, yet too much scar tissue slowly strangles the heart's ability to pump, and medicine has long lacked a way to address that excess. In a mouse study from University of Utah Health, published in Nature Communications, researchers found that quieting a single protein, AEBP1, in the cells that manufacture scar tissue kept heart failure from taking hold. The finding offers a glimpse of prevention rather than cure, a reminder that healing and harm can be made of the same material, and that timing may decide which one wins.
A heart attack asks the body to do two things at once: close the wound and keep the heart strong. Scar tissue is part of that bargain, but when the cells that produce it keep working past the point of need, the heart grows stiff and eventually fails. Most heart failure is driven in large part by this excess scarring, and no treatment yet exists to address it directly.
At University of Utah Health, researchers asked whether one protein, AEBP1, was a lever worth pulling. In mice given a heart attack, lowering AEBP1 in the scar-producing fibroblasts led to markedly better heart function four weeks later. Thirupura Shankar, the study's first author, described it as the first clear evidence that suppressing AEBP1 could stop heart failure from progressing.
The limit is equally clear. When the team lowered AEBP1 after heart failure had already set in, nothing improved. The protein appears to govern how scarring begins, not how it can be undone. Human tissue points in a similar direction: the gene runs hotter in people with advanced heart failure, and lowering the protein in donated heart samples made the tissue look healthier and less scarred.
Senior author Stavros Drakos stressed that scarring itself is not the enemy. Some early fibrosis is needed to hold the heart together, so the aim is to let healing finish before restraining the overactive cells. The open question now is timing: how long after a heart attack the scar should be allowed to form before AEBP1 is quieted. Whether this will help people has not yet been tested.
In a mouse model of heart attack, researchers at University of Utah Health kept severe heart failure from developing by turning down a single protein called AEBP1. The protein drives the formation of excess scar tissue in the heart, and the work, published in Nature Communications, points to a possible way to attack a problem that currently has no treatment.
The backdrop is a common one. Most heart failure cases are caused, to a large degree, by a build-up of excess scar tissue, known as fibrosis. No therapy exists for that scarring. The Utah team set out to see whether reducing AEBP1, which triggers it, could change the course of the disease after a heart attack or prolonged hypertension.
In the mice, it did. When the researchers lowered AEBP1 in fibroblasts, the cells that produce scar tissue, after a heart attack, heart function was significantly better four weeks later. "For the first time, we show that if we suppress AEBP1, it prevents heart failure progression and preserves cardiac function," said Thirupura Shankar, PhD, a postdoctoral researcher in the Nora Eccles Harrison Cardiovascular Research Training Institute and first author of the study.
There is a hard limit, though. When the team lowered AEBP1 after heart failure had already progressed, heart function did not improve. That suggests blocking the protein can prevent unhealthy scarring but cannot reverse it. The team also mapped some of the pathways through which AEBP1 acts, including its regulation of a variety of genes tied to unhealthy scarring, which may point to additional therapeutic targets.
Several findings suggest the protein matters in people as well. The AEBP1 gene is more active in the hearts of people with advanced heart failure, and the protein it produces is highest around areas of heart injury. In human heart tissue culture, raising AEBP1 in healthy tissue changed the appearance of heart cells in ways that resemble heart failure. Lowering it in samples donated by heart failure patients made the cellular architecture look healthier and reduced scarring.
The researchers stress that shutting down fibrosis altogether would be the wrong approach. Right after a heart attack, some scarring is needed to keep the heart structurally sound. The trouble comes when overactive fibroblasts keep making scar tissue beyond what is needed. The goal is to allow early fibrosis, then restrain the overactive cells. "Fibrosis is part of healing," said Stavros Drakos, MD, PhD, professor of medicine at U of U Health, senior author and Shankar's mentor. "We need to first complete the healing, and then do the anti-fibrotic process."
The work is still early. Shankar called for more research and long-term studies, and Drakos said future studies must determine the best timing for reducing AEBP1 to maximize heart function after a heart attack. Whether targeting the protein helps people has yet to be tested. Shankar noted that AEBP1 appears to play a promising role in other organs too, and that seeing something similar in the heart is exciting. What to watch next is the timing question: how long after a heart attack scarring should be left alone before AEBP1 is suppressed.
Citations marquantes
For the first time, we show that if we suppress AEBP1, it prevents heart failure progression and preserves cardiac function.— Thirupura Shankar, PhD, first author
Fibrosis is part of healing. We need to first complete the healing, and then do the anti-fibrotic process.— Stavros Drakos, MD, PhD, senior author
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