BCAT1 Blockade Cuts Post-MI Collagen Deposition and Preserves Ejection Fraction in Mice

The Nagoya-led group intersected stress-response transcriptomes from pressure-overload and infarction models, isolating Bcat1 among five candidates. BCAT1 protein rose selectively in myofibroblasts; its absence or pharmacologic inhibition curtailed the BCAA-to-proline axis that supplies roughly one-fifth of collagen residues. Knockout animals and ERG240-treated cohorts both showed lower Picrosirius-red staining at day 28 and smaller declines in fractional shortening.

Human explants from failing hearts and non-alcoholic fatty-liver biopsies displayed parallel BCAT1 upregulation, suggesting the mechanism is not rodent-specific. Because BCAT1 is minimally expressed in quiescent tissue, on-target toxicity may prove narrower than TGF-beta or integrin antagonists already tested in trials.

Standard post-MI fibrosis therapies remain absent; most candidates fail when dosed after the inflammatory window. ERG240’s efficacy at day seven therefore addresses a key translational gap, yet mouse infarcts lack the comorbidities and polypharmacy typical of older patients. Phase-appropriate toxicology and human-cell dose-response curves are now required before any first-in-human study.