Plate Nº 60 · recorded October 9, 2026
Health & Medicine ResearchReported finding
Blocking One Enzyme Cut Heart Scarring in Mice — Even a Week After Attack
A BCAT1 inhibitor reduced cardiac scarring and preserved heart function in mice, even when treatment began seven days after a heart attack, a new study finds.
By James Calloway3 min read677 words
In brief
- Treatment with the BCAT1 inhibitor ERG240 reduced scarring in mice even when started 7 days after a heart attack.
- Fibrosis is estimated to contribute to 45% of deaths in developed countries.
- About 20% of collagen consists of the amino acid proline, which BCAT1 helps supply.
- The study appears in the Journal of Clinical Investigation (2026), DOI: 10.1172/jci182216.
- Elevated BCAT1 levels were found in heart tissue from heart failure patients and livers of fatty liver disease patients.
A drug that blocks a single enzyme, BCAT1, reduced scar tissue in the heart and preserved pumping function in mice — even when researchers started treatment a full seven days after a simulated heart attack. The study, led by Nagoya University and published in the Journal of Clinical Investigation in 2026, points to a new way to prevent the organ stiffening that follows cardiac injury.
Heart failure often develops after a heart attack because the repair process produces too much collagen-based scar tissue. Collagen is necessary to reinforce a healing wound, but chronic inflammation and disease can push production into overdrive. The excess collagen stiffens the heart muscle and weakens its pumping. Doctors call this stiffening fibrosis, and it is a major unsolved medical problem: by some estimates, fibrosis contributes to 45% of deaths in developed countries, yet no approved therapy directly suppresses it.
What does BCAT1 actually do?
Fibrosis is driven by specialized cells called myofibroblasts, which flood injured tissue with collagen. About 20% of collagen consists of a single amino acid, proline — a building block the myofibroblasts must somehow supply in bulk.
The research team, led by Professor Michio Nakaya of Nagoya University's Research Institute of Environmental Medicine, together with colleagues at Kyushu University and Tokushima University, asked how the cells manage that supply. They compared genes activated by physical stress with genes switched on in mouse hearts after a heart attack, and found five overlapping candidates. One of them, Bcat1, stood out because nobody had studied its role in myofibroblasts before.
The results show why it matters. BCAT1 was barely detectable in healthy mouse hearts, but after a heart attack its levels rose sharply in collagen-producing cells as fibrosis progressed. The enzyme activates a cellular pathway that keeps proline flowing, effectively powering the raw-material supply line that fibrotic cells use to build collagen.
How well did blocking it work?
The researchers tested two approaches. First, they used mice genetically engineered to lack BCAT1. After a heart attack, these mice produced fewer proline-related enzymes, made less collagen, developed less scar tissue, and kept better heart function than control mice.
Second, they gave ordinary mice the BCAT1 inhibitor ERG240 after a heart attack. The drug reduced scarring and preserved heart function even when treatment began seven days after injury — during the transition from acute inflammation to the chronic phase. That timing matters, because in the real world doctors intervene after a heart attack, not before.
Nakaya said: "We found that BCAT1 is a new driver of excessive collagen production in the fibrotic heart by increasing the supply of proline, a major building block of collagen. Importantly, pharmacological inhibition of BCAT1 suppressed cardiac fibrosis and preserved cardiac function, even when treatment started after fibrosis had begun to develop."
Could this work in humans?
The mouse data are not the only signal. When the team analyzed heart tissue from patients with heart failure, they found elevated BCAT1 levels associated with increased fibrosis, suggesting a similar mechanism operates in humans. Livers from patients with fatty liver disease also showed higher BCAT1, hinting the approach could extend beyond the heart to fibrosis in other organs, such as the liver, where the process can progress to cirrhosis.
The safety profile is a key attraction. Because BCAT1 is largely absent from healthy tissue and mainly active in scar-forming cells, targeting it may avoid damaging normal tissue — potentially fewer side effects than existing antifibrotic approaches.
What comes next?
The findings remain preliminary. The study covered mice and tissue samples, not a clinical trial in patients, and the effective dose, safety, and long-term effects of BCAT1 inhibitors in humans are unknown.
The researchers plan two next steps:
- Determine whether the BCAT1–proline pathway also drives fibrosis in the liver and other organs.
- Develop clinically applicable BCAT1-targeted therapies and assess their safety, optimal dosing, and efficacy.
The paper is: Noburo Takizawa et al., "Branched-chain amino acid transaminase 1–mediated pathway promotes proline-dependent collagen production in cardiac myofibroblasts," Journal of Clinical Investigation (2026). DOI: 10.1172/jci182216.
via Medical Xpress (Source)
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