Abstract 19009: Increased Endogenous C-kit+ Cardiac Stem Cells Diminish Myocardial Infarction Damage in S-nitrosoglutathione Reductase Mice
Background. Cardiac tissue has endogenous cardiac stem cells (CSCs), which proliferate after myocardial infarction (MI) to support cardiac repair. As mice deficient in S-nitrosoglutathione reductase (GSNOR−/−), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI, we hypothesized that GSNOR−/− mice have higher levels of endogenous c-kit+ CSCs post-MI.
Methods. GSNOR−/− and WT (C57BL/6) mice were infarcted by permanent occlusion of the left anterior descending coronary artery. Cardiac performance was assessed by serial echocardiography. Histological sections were analyzed for infarct size and endogenous c-kit+/CD45- CSCs were quantified by immunostaining.
Results. There was no difference in ejection fraction (EF%) or endocardial volume (EDV, ESV) at baseline or 1 week post-MI, but at 8 weeks, EF% was improved (30.4±2.2 vs. 21.4±2.8, p<0.05) and EDV and ESV were preserved in GSNOR−/− mice compared with WT (ESV 72.7±6.0 vs. 139.6±19.7 ul; p<0.001, and EDV, 102.1±7.0 vs. 169.7±19.0 ul; p<0.001, respectively). In addition, GSNOR−/− mice exhibited smaller scar size (34.6±2.8 vs. 62.2±7.9%, p<0.05). The number of c-kit+/CD45- CSCs was greater in post-MI GSNOR−/− hearts vs WT, independent of the zone analyzed (infarct+border zone: 6.3±0.8 vs. 2.3±0.9 cells/mm3, p<0.05; remote zone: 0.4±0.1 vs. 0.1±0.05 cells/mm3, p<0.05).
Conclusion. Following MI, GSNOR−/− mice have preserved cardiac function, decreased remodeling and infarct size and increased c-kit+/CD45- CSCs population in cardiac tissue during the remodeling phase. Thus, c-kit+ CSCs contribute to cardioprotection in GSNOR−/− mice following MI, and suggest that enhanced S-nitrosylation based signaling contributes to CSC function following injury.
- © 2012 by American Heart Association, Inc.