Abstract 11820: NG2+ Cells Protect Against Cardiac Remodeling and Failure After Myocardial Infarction in Mice

Abstract

Introduction: Myocardial infarction kills cells, leading to cardiac remodeling (CR) and heart failure. Pericytes are microvascular mural cells that have been recently shown to have plasticity and cardiac regenerative potential, and also to interfere with CR, yet different niches present in cardiac tissue together with many cell markers that characterize resident pericytes have raised interrogate regarding their cell-specific differentiation capabilities. NG2 is a cell trans-membrane proteoglycan receptor and the most robust marker for pericytes. NG2 is normally present in embryonic cardiac myocytes, but in the adult heart its expression is only limited to pericytes and pericyte-like cells. Hypothesis: NG2+ cells are protective after myocardial infarction in the adult heart. Methods: Myocardial infarction (MI) was performed by coronary artery ligation in double transgenic mice (NG2cre-Z/EG) that express NG2-GFP under cre-lox technology, in mice lacking NG2 (NG2 -/-), and in wilt type littermate controls (WT). Cardiac histology was performed using Masson staining for fibrosis (Optical) and immunohistochemistry (Confocal) microscopy. Cardiac function was assessed by fractional shortening (FS) determined by echocardiography. Results: 7 days after MI, NG2 positive cardiac myocytes were seen in the double transgenic mice (co-staining with alpha-sarcomeric actinin) more abundantly in the infarct border zone (confocal microscopy), as opposed to those subjected to sham MI, in which NG2+ cells were mainly limited to pericytes (192 ± 26 vs 1730 ± 290 NG2+ve cardiac myocytes/cm2; p <0.001). Cardiac function deteriorated more after 4 weeks in NG2-/- compared to WT (FS = 21 ± 2.1 vs. 12.5 ± 1.1 %, WT and NG2 -/- respectively; p < 0.001). Histologic examination of cardiac tissue revealed more interstitial fibrosis in the NG2-/- hearts (1.1 ± 0.2 vs 2.3 ± 0.3 %, WT and NG2-/-), seen mainly in the remote infarct zone. Quantitative analysis (qPCR) in different progenitor cell lines also revealed co-expression of NG2 with ISL-1, a robust cardiac stem cell marker. Conclusions: Our findings indicate that NG2+ cells play a key role in post-MI cardiac remodeling, and suggest a potential therapeutic role of resident NG2+ cells in HF.