期刊
BASIC RESEARCH IN CARDIOLOGY
卷 115, 期 6, 页码 -出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-020-00821-z
关键词
Neuraminidase 1; Sialidase 1; Ischemia; reperfusion; Inflammation; Monocytes
资金
- Projekt DEAL
- Deutsche Forschungsgemeinschaft [HI 842/8-1]
- Rebirth [ZN3440]
Neuraminidase (NEU)1 forms a multienzyme complex with beta-galactosidase (beta-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, beta-GAL and PPCA expression. Mice hypomorphic forneu1(hNEU1) had less neuraminidase activity, fewer pro-inflammatory (Lin(-)CD11b(+)F4/80(+)Ly-6C(high)), and more anti-inflammatory macrophages (Lin(-)CD11b(+)F4/80(+)Ly-6C(low)) 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.
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