imprint:
Springer Science and Business Media LLC, 2020
Published in:Basic Research in Cardiology
Language:
English
DOI:
10.1007/s00395-020-00821-z
ISSN:
0300-8428;
1435-1803
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>Neuraminidase (NEU)1 forms a multienzyme complex with beta-galactosidase (β-GAL) and protective-protein/cathepsin (PPC) A, which cleaves sialic-acids from cell surface glycoconjugates. We investigated the role of NEU1 in the myocardium after ischemia/reperfusion (I/R). Three days after inducing I/R, left ventricles (LV) of male mice (3 months-old) displayed upregulated neuraminidase activity and increased NEU1, β-GAL and PPCA expression. Mice hypomorphic for<jats:italic>neu1</jats:italic>(hNEU1) had less neuraminidase activity, fewer pro-inflammatory (Lin<jats:sup>−</jats:sup>CD11b<jats:sup>+</jats:sup>F4/80<jats:sup>+</jats:sup>Ly-6C<jats:sup>high</jats:sup>), and more anti-inflammatory macrophages (Lin<jats:sup>−</jats:sup>CD11b<jats:sup>+</jats:sup>F4/80<jats:sup>+</jats:sup>Ly-6C<jats:sup>low</jats:sup>) 3 days after I/R, and less LV dysfunction 14 days after I/R. WT mice transplanted with hNEU1-bone marrow (BM) and hNEU1 mice with WT-BM showed significantly better LV function 14 days after I/R compared with WT mice with WT-BM. Mice with a cardiomyocyte-specific NEU1 overexpression displayed no difference in inflammation 3 days after I/R, but showed increased cardiomyocyte hypertrophy, reduced expression and mislocalization of Connexin-43 in gap junctions, and LV dysfunction despite a similar infarct scar size to WT mice 14 days after I/R. The upregulation of NEU1 after I/R contributes to heart failure by promoting inflammation in invading monocytes/macrophages, enhancing cardiomyocyte hypertrophy, and impairing gap junction function, suggesting that systemic NEU1 inhibition may reduce heart failure after I/R.</jats:p>