Latent Transforming Growth Factor Binding Protein ? 2 promotes microfibrillar TGF-? bioavailability to drive pathologic fibrosis in remote regions of infarcted hearts

Deleting Ltbp2 in mice after permanent coronary ligation improves 28-day survival (P=0.0272) and preserves remote myocardium function by reducing interstitial collagen and stiffness.

• Why it matters: Remote remodeling after myocardial infarction drives progressive dysfunction, yet it is unclear how an injury-induced microfibril ECM protein that lacks latent TGF-β binding capacity can still amplify TGF-β–dependent fibrosis.
• What they did: Wild-type and Ltbp2-null mice were followed 28 days post-MI with echocardiography and strain; remote tissue was analyzed by histology, atomic force microscopy, and quantitative proteomics, with fibroblast TGF-β reporter assays and sufficiency tests using a fibrillin-1–binding LTBP2 module.
• The result: Ltbp2 loss attenuated ECM organization and TGF-β–responsive programs, increased LTBP1 matrix incorporation, shifted TGF-β toward matrix-bound forms, and the minimal LTBP2 module mobilized latent TGF-β from established matrix within 20 minutes.

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