Work

Targeting lysozyme 2 in endocardium promotes rapid recovery by modulating remote injury signals

Year: 2025

Type: article

Abstract: Adult mammalian hearts are non-regenerative, and a majority of studies examining repair and potential regeneration post-myocardial infarction (MI) have focused on cardiomyocyte (CM) proliferation and infarcted zones. Here, we observed aberrantly high expression of lysozyme 2 (Lyz2) in injured mouse hearts at both local injury sites and at remote zones, with sustained Lyz2 expression conspicuous in endocardial cells of non-regenerative hearts. Although traditionally conceptualized as a myeloid marker, we demonstrate that LYZ2 functions as an injury-specific, positive regulator of lysosomal degradation capacity that mediates pathogenic degradation of the extracellular matrix. We observed an anti-apoptotic benefit to CMs upon disrupting LYZ2/LYZ function in mice and in a human endomyocardium experimental model. Harnessing these insights, we show that both Lyz2 knockout (KO) and pharmacological inhibition of lysosomal degradation confer rapid functional recovery in injured non-regenerative hearts. Thus, targeting a remote injury response in a non-CM cell type rapidly promotes post-MI recovery of non-regenerative hearts.

Source: Cell stem cell

DOI: 10.1016/j.stem.2025.08.015